Exploring the multi-dimensional free energy
surface of phosphoester hydrolysis with
constrained QM/MM dynamics
Wenjin Li,1,2 Till Rudack,3 Klaus Gerwert,1,2 Frauke Gräter,∗,1,2 and Jürgen Schlitter∗,3
1 CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai
Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai
200031, China.
2 Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg,
Germany.
3 Ruhr-Universität Bochum, Lehrstuhl für Biophysik ND 04, 44780 Bochum, Germany.
∗ Corresponding author: [email protected], [email protected]
Supplementary Materials
Multi-dimensional Potential of Mean Constraint Force (MPMCF)
As the theory of MPMCF is given in the main text, we demonstrate here how to derive the free
energy surface using a simple two-dimensional example. Then, the application to multi-dimensional
force is straightforward. Meanwhile, we show how we derive Eq.(3) from Eq. (2).
Before giving the general formula for free energy calculation of multi-dimensional space, we
show an example of obtaining a two-dimensional free energy surface using Eq. (2). As shown in
Figure S1, r1 and r2 are the two coordinates to which the constraints are added. Then, according
to Eq. (2), we have,
∂
∂A
= hf1c ic − kB T
lnh(det(z)−1/2 )ic
∂r1
∂r1
(1)
∂A
∂
= hf2c ic − kB T
lnh(det(z)−1/2 )ic
∂r2
∂r2
(2)
fic ≡ λri is the constraint force along ri . Assume A and B are two points in the two-dimensional
space of r1 and r2 , and A is at (r1a , r2a ) and B is at (r1b , r2b ) (see Figure S1). Then, there are two
pathways along which to integrate. One is the blue path, A→C→B, and is colored blue. The other
one is the red path A→D→B, and is colored red.
Let’s integrate along the blue path. Then, the free energy difference between A and B is given
S1
by,
A(r1b , r2b ) − A(r1a , r2a ) = (A(r1b , r2a ) − A(r1a , r2a )) + (A(r1b , r2b ) − A(r1b , r2a ))
Z rb2
Z r1b
∂A
∂A
dr1 +
dr2
=
a
a
∂r
∂r
1
2
r2
r1
Z r1b
Z rb2
(rb ,ra )
=
hf1c ic dr1 − kB Tlnh(det(z)−1/2 )ic |(r1a ,ra2) +
hf2c ic dr2
1
r1a
2
ra2
(rb ,rb )
− kB T lnh(det(z)−1/2 )ic |(rb1 ,ra2 )
1 2
Z r1b
Z rb2
(rb ,rb )
=
hf1c ic dr1 +
hf2c ic dr2 − kB Tlnh(det(z)−1/2 )ic |(ra1 ,ra2)
r1a
ra2
1
(3)
2
Clearly, the free energy difference between points A and B obtained by integral along the blue
path is the same as that obtained by integral along the red path. Numerically, the blue and the
red paths are two typical paths since one can fix one coordinate and integrate along the other. A
comparison of the results obtained for the two paths provides a check of numerical integration. For
the two-dimensional case, therefore, free energy is calculated as
A2 (r1 , r2 ) =
2 Z
X
hfαc ic drα − kB T lnh(det(z)−1/2 )ic
(4)
α=1
and the generalization to a n-dimensional subspace reads
An (r1 , ..., rn ) =
n Z
X
hfαc ic drα − kB T lnh(det(z)−1/2 )ic
(5)
α=1
The practical computation starts by defining an equidistant grid on which the mean constraint
forces and the Fixmann determinant are determined numerically. Free energy is subsequently
generated on the same grid by numerical integration.
We have implemented the MPMCF into Gromacs-4.0.7, 1 and tested it on several simple systems
to ensure the success of the implementation (data not shown).
Free energy surfaces obtained from different metastable states
In this section, we explain how to construct a two-dimensional free energy landscape by MPMCF.
The free energy landscape is represented by 35×35 points on a rectangular grid (see Fig. S8), each
of which represents an equilibrium structure with given values of the constrained coordinate, R1
and R2. Here, R1 takes the value of 1.64 Å, 1.68 Å, 1.72 Å, 1.76 Å, 1.8 Å, 1.84 Å, 1.88 Å, 1.92 Å,
1.96 Å, 2 Å, 2.04 Å, 2.08 Å, 2.12 Å, 2.16 Å, 2.2 Å, 2.25 Å, 2.3 Å, 2.35 Å, 2.4 Å, 2.45 Å, 2.5 Å, 2.55 Å,
2.6 Å, 2.65 Å, 2.7 Å, 2.8 Å, 2.9 Å, 3 Å, 3.1 Å, 3.2 Å, 3.3 Å, 3.4 Å, 3.5 Å, 3.6 Å and 3.7 Å, and R2 takes
the value of 1.64 Å, 1.66 Å, 1.68 Å, 1.72 Å, 1.76 Å, 1.8 Å, 1.84 Å, 1.88 Å, 1.92 Å, 1.96 Å, 2 Å, 2.04 Å,
S2
2.08 Å, 2.12 Å, 2.16 Å, 2.2 Å, 2.25 Å, 2.3 Å, 2.35 Å, 2.4 Å, 2.45 Å, 2.5 Å, 2.55 Å, 2.6 Å, 2.65 Å, 2.7 Å,
2.8 Å, 2.9 Å, 3 Å, 3.1 Å, 3.2 Å, 3.3 Å, 3.4 Å, 3.5 Å and 3.6 Å. There are three steps in constructing a
two-dimensional free energy landscape on R1 and R2 using MPMCF. First, starting with an initial
structure, construct a structure with given values of R1 and R2 for each point on the grid (there
are 35 × 35 = 1225 structures in total) following a defined route. Secondly, for each point on the
grid, start from the structure obtained in the previous step (let’s call it ”starting structure”) and
run an 1ps QMMM simulation in a level of B3LYP (basis set: 6-31G*) with constraints on R1 and
R2 at given values. From these, the mean constraint force (hfαc ic in Eq. (3)) and the Fixmann
determinant (Z in Eq. (3)) are then evaluated. Thirdly, along the defined route that is used to
generate starting structures for each point on the grid in the first step, integrate the resulted hfαc ic
to obtain the relative free energy of each point on the grid and then correct it with the Fixmann
determinant (as indicated in Eq. (3)).
The free energy landscapes shown in Fig. 2 are constructed in ways, which can differ in the
initial structure and/or the defined route. The initial structures and the defined routes that are
used to construct the FES’s in Fig. 2 are shown in Table S3 and the defined route for Fig. 2A is
shown explicitly in Fig. S8. The three steps to construct the FES are explained below.
1) Start from an initial structure and construct a structure with given values of R1
and R2 for each point on the grid
To generate all of the starting structures in the points on the grid from a single initial structure,
we first generate starting structures following a path along one coordinate (called ”first-coordinate
path” and may be along either R1 or R2). In the case of Fig. 2A, the ”first-coordinate path” is
the red line shown in Fig. S8 (for the points on the path, see Table S3). Then, starting from the
structures obtained in the previous step, we generate starting structures following paths along the
other coordinate (this is called the ”second-coordinate paths”). In the case of Fig. 2A, the green
lines shown in Fig. S8 are the ”second-coordinate paths” (for the points on the paths see Table
S3). Take the case of Fig. 2A as an example for a detailed explanation.
a) Generate starting structures for the points in the ”first-coordinate path”. In the
case of Fig. 2A, we first generate starting structures along R2. That is to say, we keep the value of
R1 unchanged and vary the value of R2. The initial structure is a structure with R1=1.80 Å and
R2=3.60 Å (as shown in the list of ”Initial structure” in the column of ”Fig. 2A” in Table S3).
First, starting with the initial structure, we run a 100fs-simulation by constraining the structure at
R1=1.80 Å and R2=3.60 Å, the first point in the ”first-coordinate path”. The last structure in the
simulation is taken as the starting structure for the point R1=1.80 Å and R2=3.60 Å. Then, using
the starting structure at the point R1=1.80 Å and R2=3.60 Å obtained in the previous step, we run
S3
again a 100fs-simulation by constraining the structure at R1=1.80 Å and R2=3.50 Å. This is the
second point in the list of ”first-coordinate path”. Next, repeat the previous step to generate other
starting structures for the point in the list of ”first-coordinate path”. So, the order to generate the
starting structure is from the top to the bottom of the ”first-coordinate paths” list in Table S3, or
from the top to the bottom of the red line in Fig. S8.
b) Generate starting structures for the points in the ”second-coordinate paths”.
After obtaining the 35 starting structures along R2 in the previous step, we keep the value of
R2 unchanged and change the value of R1 forward and/or backward. Taking R2=3.60 Å as an
example, forward (backward) means to constrain the system at states sequentially with values
of R1 and R2 listed explicitly in the ”forward” (”backward”) list of ”second-coordinate paths”.
Like generating starting structures along R2, we take the starting structure at R1=1.80 Å and
R2=3.60 Å, and generate the structures in the list of ”second-coordinate paths” along R1 one by
one. There are 35 ”second-coordinate paths” (the green lines in Fig. S8), but only the one at the
top appears in Table S3.
2) Start with the structures obtained in the previous step and run a product simulation.
In the previous step, we constructed all the starting structures for each point on the grid. Now, for
each point on the grid, we run a 1ps QMMM simulation at the level of B3LYP (basis set: 6-31G*)
with constraints on R1 and R2 at given values. Then, the mean constraint force on R1 and R2 at
each point can be estimated, as well as the Fixmann determinant.
3) Integrate the constraint mean force along the defined route to get the relative free
energy at each point.
Using Eq. (3), we integrate along the paths listed in Table S6 (the same one along which we
evolve the system to obtain the starting structures), and construct the two-dimensional free energy
landscape. Taking Fig. 2A as an example, first integrate along the ”first-coordinate path” (the
red line in Fig. S8) to obtain the free energy along R2 at R1=1.80 Å. Here, we take the mean
constraint forces along R2 only. Then, Integrate along the ”second-coordinate paths” (the green
lines in Fig. S8) to obtain the free energy along R1 at various values of R2. Here, we take the
mean constraint forces along R1 only. Finally, connect the 35 free energy curves along R1 with
that along R2 at the cross point between them. Now, a two-dimensional free energy surface has
been constructed.
Why do we integrate the constraint mean force along the defined route to obtain the free
energy landscape? As stated before, the free energy difference between two points on the free
S4
energy surface is independent of the integral route and one should obtain the same free energy
surface no matter which integral route is taken. This is only true if all important coordinates are
taken into account. If not, the mean constraint forces obtained along different routes can be quite
different. As we constrain only R1 and R2 here, the starting structures obtained from different
route may share the same values of R1 and R2, but may differ in other important coordinates.
These differences may make significant differences in the mean constraint forces. So, given that not
all important coordinates have been taken into account, only the free energy curve obtained along
the same route as that one generating the starting structures is meaningful. To better visualize the
results, all of the resulting free energy surfaces are shifted to let the lowest free energy approximate
zero (see Fig. 2 and Table S4).
A complete associative pathway
How does one construct a free energy landscape along a path in a multi-dimensional path by
MPMCF? The path is simply an ordered sequence of states, P (N ) ≡ {X1 , X2 , ..., XN } (see Tables
S1 and S2). 1) Firstly, we run an 100fs simulation by constraining the structure at X1 . Then, we
take the last structure of the previous simulation and run another 100fs simulation by constraining
the structure at X2 . Repeat this until all N structures have been obtained. 2) Then for each pair of
structures (Xi and Xi+1 ), we run a 1ps simulation by constraining the system at Xi starting from
the structure obtained at Xi in step (1). Take the end structure and run another 1ps simulation
by constraining the system at Xi+1 . We also run a 1ps-simulation by constraining the system at
Xi+1 starting from the structure obtained at Xi+1 in step (1) and then taking the end structure
and running another 1ps-simulation by constraining the system at Xi . The step from Xi to Xi+1
is called the forward step and the one from Xi+1 to Xi is termed the backward step. The mean
constraint force (MCF) is then estimated by averaging the constraint force over each 1ps simulation.
For each point in the path, we obtained four MCF’s except the two end points (of which there are
two). The MCF’s obtained by forward and backward steps are consistent.
The evaluation of the free energy landscape along a path can be divided into several sections
since the multi-dimensional path usually consists of several segments, with only one coordinate
change in each segment. For each segment, the average MCF is obtained by cubic spline fitting
to all of the MCF’s along the coordinate. The free energy of each segment can be estimated easily by integrating the MCF along this coordinate. Then, the free energy along the entire path
can be constructed by connecting the free energies of all segments. Take a path connecting point
R1=1.80 Å, R2=2.20 Å and point R1=1.80 Å, R2=2.12 Å as an example. The path involves proton
transfer.) (See ’Case A’ of step II in Table S1) The path can be divided into two segments. One
is from point R1=1.80 Å, R2=2.20 Å to point R1=1.80 Å, R2=2.12 Å without the transfer of pro-
S5
ton from the water to the phosphate group (the first four points). The other is from R1=1.80 Å,
R2=2.12 Å, X=-2.10 Å2 to R1=1.80 Å, R2=2.12 Å, X=1.95 Å2 (the last 20 points, point R1=1.80 Å,
R2=2.12 Å, X=-2.10 Å2 overlaps point R1=1.80 Å, R2=2.12 Å). It may be noted that the first segment involves only two coordinate, whereas the second involves three coordinates. How can these
two segments be connected? In practice, we have evaluated the free energy landscape along X
from X=-4.4 Å2 to X=4.4 Å2 , while keeping R1 and R2 invariant. The whole energy landscape
is shown in Fig. S6. There are two local minima at X=-2.10 Å2 and X=1.95 Å2 and the most
populated states during the simulation by restraining R1 at 1.80 Å and R2 at 2.12 Å only should
locate at these two minima. So the two segments are continuous at point R1=1.80 Å, R2=2.12 Å,
X=-2.10 Å2 and we can simply connect them to obtain the free energy landscape of the entire
path. We also compared the MCF’s obtained along R1 and R2 by constraining three coordinates at R1=1.80 Å, R2=2.12 Å, X=-2.10 Å2 and thus obtained by constraining two coordinates at
R1=1.80 Å, R2=2.12 Å( the proton doesn’t transfer) and discovered that they are consistent with
each other. The same is true between the MCF’s along R1 and R2 that were obtained by constraining three coordinates at R1=1.80 Å, R2=2.12 Å, X=1.95 Å2 and those obtained by constraining
two coordinates at R1=1.80 Å, R2=2.12 Å(the proton transfers to the phosphate group).
An estimation of the 2-D free energy surface
The construction of FES in Fig. 4
Since not all of the vital coordinates are taken into account, only part of the free energy surfaces
(FES) shown in Fig. 2 (for example, the lower-left triangular part of the FES’s in Fig. 2A and Fig.
2B and the upper-right triangular part of the FES’s in Fig. 2E and Fig. 2F) are well resolved.
One can combine these parts together to obtain a more accurate picture of the FES. Note that the
real FES should consist of the lowest free energy projects on R1 and R2, as the chemical reactions
occur along the lowest free energy path. So, for each point on the grid, one can take the lowest
free energy from two FES’s to construct an FES closer to the real one. For FES’s in Fig. 2A and
Fig. 2B, they are integrated from the same initial point (the point referred to the initial structure,
with R1=1.80 Å, R2=3.60 Å). In other words, the two FES’s are referred to the same free energy
reference point and are comparable. We simply take the lower of the two FES’s at each point
to construct a more accurate FES (RS-FES), especially for the lower-left triangular part of the
actual FES. Similarly, the FES’s in Fig. 2E and Fig. 2D are referred to the same free energy
point (R1=3.30 Å, R2=1.80 Å). By combining the two FES’s in the same way, we obtain an FES
(PS-FES) with accurate upper-right triangular part.
Now, the question is how to combine the RS-FES and PS-FES into one FES, given that they are
referred to different free energy points? If we know the free energy difference between the two free
S6
energy reference points, we can shift the FES’s to make sure that they are referred to the same free
energy reference. As the free landscape shown in Fig. 3 is carefully estimated by taking all the vital
coordinates into account, the free energy landscape is very accurate and can be used as a reference.
From Fig. 3, we know that the free energy at the point R1=1.72 Å, R2=3.60 Å is 1.69 kcal/mol
higher than that at the point R1=3.70 Å, R2=1.72 Å (see Table S1). Therefore, we shift PS-FES
to ensure that the free energy at point R1=1.72 Å, R2=3.60 Å in RS-FES is 1.69 kcal/mol higher
than that at point R1=3.70 Å, R2=1.72 Å in PS-FES. Now, the two FES’s are referred to the same
free energy reference and can be compared. By taking the lower free energy from the two FES’s,
the final FES has been constructed and appears in Fig. 4. As may be noted, the two reference
points chosen here (R1=1.72 Å, R2=3.60 Å and R1=3.70 Å, R2=1.72 Å) differ from the two initial
points (R1=1.80 Å, R2=3.60 Åand R1=3.30 Å, R2=1.80 Å). However, they are within the same
two metastable states. Point R1=1.72 Å, R2=3.60 Å and point R1=1.80 Å, R2=3.60 Å belong to
the reactant region, while point R1=3.70 Å, R2=1.72 Å and point R1=3.30 Å, R2=1.80 Å belong
to the product region. So, it must make no difference to the final FES that is constructed by
referring to the two points instead of the two initial points.
Other quantitatively resolved 2D free energy surface
Similarly, by shifting FES’s in Fig. 2C and Fig. 2D to ensure that the free energy difference
between the point R1=1.84 Å, R2=2.00 Å in Fig. 2C and the point R1=2.00 Å, R2=1.80 Å in Fig.
2D is the same as that between the same point in the proposed associative path (see Table S1.
The free energy at R1=2.00 Å, R2=1.80 Å minus the one at R1=1.84 Å, R2=2.00 Å is 1.0 kcal/mol.
We take these two points as the reference points, because they are the two representative points
before and after the rotation of the O-H bond.). Then, taking the lowest free energy at each point,
we constructed a two-dimensional FES along R1 and R2 (see Fig. S2). The free energy surface
estimated here is quite similar to the one shown in Fig. 4. The exact numbers of the free energy
are different, which is due to the differences in the positions where the proton transfers. This FES
didn’t take the coordinate of proton transfer and the rotation of the O-H bond into account. Thus,
the free energy shown here is not as reliable as that shown in Fig. 3. If one is not considering the
rotation of the O-H bond, the top-left region of the FES is resolved reliably. The free energy of the
transition state in Fig. S2 is about 39kcal/mol and its more accurate estimate at the same point
in Fig. 3 is 42.5kcal/mol.
Transition path sampling
Order parameter and initial path.
Transition path sampling (TPS) is a powerful method
to investigate rare events, such as (bio)chemical reactions and protein foldings, which usually
S7
involve high free-energy barrier. 2 Starting from an initial reactive path (not necessarily physically
meaningful), one can randomly sample the reactive paths using Monte Carlo criteria and finally
find the reactive paths that are energetically favored. To conduct transition path sampling, one
needs to define two metastable states according to one, or several, order parameters, which need
not be good reaction coordinates. Here, four order parameters - R1, R2, X2 and X4, which shown
in Fig. S3 - are used to define the reactant state (RS) and product state (PS). The RS region is
the region with R1≤1.80 Å, R2≥2.80 Å, X2≤1.10 Å and X4≤1.10 Å, and the PS region is one with
R1≥3.00 Å, R2≤1.80 Å, X2≥1.50 Å and X4≤1.10 Å.
An initial reactive trajectory was necessary to initiate TPS. It is generated as follows. By
imposing a distance restraint to R2 with an equilibrium distance of 1.60 Å and a spring constant
of 10,000 kJ mol−1 nm−2 , the nucleophilic water was forced to attack the phosphate group and the
hydrolysis occurred within 3 ps via an associative-like path. From this resulting reactive path,
we selected several structures, which were thought to be similar to the transition state, and then
randomly shot many trajectories from these structures. If the simulation ended in RS (PS), we
reversed the momentum of the starting structure and did MD simulations to see whether it relaxes
to PS (RS). If so, the initial reactive path for TPS was then obtained.
Sampling.
To enhance the efficiency of TPS, shooting moves, shifting moves and diffusion
moves 3 were applied in a ratio of 1:1:1. The acceptance ratio for shooting and shifting moves
are adjusted to about 40% by changing the momentum displacement and the time displacement,
respectively. The simulation is 600 fs in length for each transition path.
Results.
The software used for TPS is the one that was implemented into gromacs in our
group and has been demonstrated to be a success in a previous study. 4 In 900 attempts of TPS,
we obtained 206 reactive trajectories following an associative pathway. A representative example
is shown in Fig. S4. As shown in Fig. S4, the proton transfers from the attacking water to the
phosphate group directly and at almost the same time at which the OW -P bond forms. The final
structure of the simulation (structure d) is not the product state that we expected, because HPT
doesn’t transfers to the methyl group. This product is the same as the one in Fig. 2A (the upper
right region, the structure is not shown) and we believe that the reactive paths that were sampled
by TPS follow the free energy surface shown in Fig. 2A. However, the paths from RS to the state
after HPT transferred from OW to OP (from structure a to structure c via structure b) is the same
as the one following the correct associative pathway. We can find where the proton transfer takes
place from these reactive paths. The structures with 1.15 Å≤X1≤1.30 Å and 1.15 Å≤X2≤1.30 Å
were considered to be the structures at which the proton transfer takes place and are screened
from the reactive paths sampled. The distribution of their values of R1 and R2 are shown in Fig.
S8
S5A and Fig. S5B, respectively. So the proton transfer occurs on average at R1=1.71±0.05 Å and
R2=2.54±0.12 Å.
S9
Supplementary figures
Figure S1: A scratch of two-dimensional integration in two-dimensional space.
Figure S2: Free energy surface along R1 and R2. It is constructed by combining the free
energy surfaces shown in Fig. 2C and Fig. 2D. The details are explained above.
S10
Figure S3: Description of important coordinates. R1, R2 and X2 are explained in the main
text (see Fig. 1). X4 is the distance between OW and the other proton of the water (not HPT ).
Figure S4: An example of the transition path. Four important coordinates (R1, R2, X2 and
X4, shown in Fig. S3) are shown over time. Structures a, b, c and d are four structures taken at
time 0.03 ps, 0.056 ps, 0.22 ps and 0.552 ps, respectively (shown as dashed lines in yellow, brown,
grey and violet, respectively). The value of R1 and R2 for each structure are shown in the form of
[R1,R2].
S11
Figure S5: The distribution of R1 and R2 when the proton transfers. A and B are the
distributions of R1 and R2 when the proton transfers from the nucleophilic water to the phosphate
group, respectively. The distribution of R1 and R2 are averaged at 1.71±0.05 Å and 2.54±0.12 Å,
respectively.
Figure S6: Free energy along X. The region between X=-2.10 and X=1.95 (highlighted as
dashed lines in grey and brown, respectively) are taken into the free energy landscape along the
whole associative path.
S12
Figure S7: The free energy barrier of the proton transfer at different points. A: the
free energy barrier during HPT transfers from OW to OP at different points along R2. B: the free
energy barrier during HPT transfers from OP to OM at different points along R1. We assume a
linear change of the free energy barrier along the coordinate and a line is fitted in each plot. Black
circles: the simulation data, red line: the fitting line.
Figure S8: The grid of points to represent the free energy surface 35×35 points on a
rectangular grid are used to represent the 2-D free energy surface along R1 and R2. Here, R1 takes
the value of 1.64 Å, 1.68 Å, 1.72 Å, 1.76 Å, 1.8 Å, 1.84 Å, 1.88 Å, 1.92 Å, 1.96 Å, 2 Å, 2.04 Å, 2.08 Å,
2.12 Å, 2.16 Å, 2.2 Å, 2.25 Å, 2.3 Å, 2.35 Å, 2.4 Å, 2.45 Å, 2.5 Å, 2.55 Å, 2.6 Å, 2.65 Å, 2.7 Å, 2.8 Å,
2.9 Å, 3 Å, 3.1 Å, 3.2 Å, 3.3 Å, 3.4 Å, 3.5 Å, 3.6 Å and 3.7 Å, and R2 takes the value of 1.64 Å, 1.66 Å,
1.68 Å, 1.72 Å, 1.76 Å, 1.8 Å, 1.84 Å, 1.88 Å, 1.92 Å, 1.96 Å, 2 Å, 2.04 Å, 2.08 Å, 2.12 Å, 2.16 Å, 2.2 Å,
2.25 Å, 2.3 Å, 2.35 Å, 2.4 Å, 2.45 Å, 2.5 Å, 2.55 Å, 2.6 Å, 2.65 Å, 2.7 Å, 2.8 Å, 2.9 Å, 3 Å, 3.1 Å, 3.2 Å,
3.3 Å, 3.4 Å, 3.5 Å and 3.6 Å. The defined route to generate starting structures and construct the
2-D free energy surface in Fig. 2A are shown as well. In Fig. 2A, we first generate the starting
structures for the points in the red line, which corresponds to the ”first-coordinate path” in Table
S3. Then we generate the starting structures for the points in the green lines, which correspond
to the ”second-coordinate paths” in Table S3.
S13
Supplementary Tables
S14
Table S1: The proposed associative paths and the free energy. The table shows the
data in Fig. 3. The points in the proposed associative path, their index and their free energies
are listed. If the column in R3 is blank, the simulation is done by constraining only R1 and
R2. R3 represents X, Y and Z in steps 2, 4 and 6, respectively. Coordinates R1, R2, X, Y and
Z are explained in the main text. If the value of R3 is in ”[]”, it means that the two points,
one with two coordinate and the other with three coordinate overlap. In steps II, IV and VI,
the free energies of the last point are estimated by averaging all of the results available. Their
free energies are 41.28±0.84 kcal/mol, 42.46±0.61 kcal/mol and 34.72±0.38 kcal/mol, respectively.
The free energy is in units of kcal/mol. The simulation is divided into ten parts, over which
ten free energy landscapes are estimated and the average and standard deviation are then evaluated.
index
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
R1
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.76
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
R2
3.60
3.50
3.40
3.30
3.20
3.10
3.00
2.90
2.80
2.70
2.70
2.70
2.70
2.65
2.60
2.55
2.50
2.45
2.40
2.35
2.30
2.25
2.20
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
R1
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
R2
2.20
2.16
2.14
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
2.12
45
46
47
48
49
R1
1.80
1.80
1.80
1.80
1.84
R2
2.12
2.08
2.04
2.00
2.00
Step I
R3
ave+/-std
0.00
0.36
0.73
0.40
1.48
0.37
2.00
0.23
2.63
0.18
3.56
0.18
4.93
0.15
6.77
0.08
9.04
0.04
12.17 0.10
12.17 0.10
12.57 0.08
13.47 0.08
15.30 0.11
17.34 0.17
19.45 0.19
21.62 0.19
23.82 0.22
26.10 0.17
28.32 0.15
30.59 0.14
33.17 0.08
35.79 0.06
Case A
R3
ave+/-std
35.79 0.06
37.99 0.07
39.15 0.08
[-2.1] 40.31 0.10
-1.80 40.36 0.41
-1.49 40.52 0.30
-1.19 40.96 0.24
-1.03 41.33 0.22
-0.88 41.76 0.20
-0.57 42.70 0.15
-0.42 43.22 0.13
-0.27 43.62 0.11
-0.11 43.81 0.10
0.04
43.84 0.11
0.19
43.74 0.09
0.34
43.58 0.08
0.50
43.34 0.12
0.65
43.01 0.21
0.80
42.58 0.31
1.11
41.57 0.38
1.57
40.84 0.35
1.72
40.71 0.37
[1.95] 40.66 0.36
Step III
R3
ave+/-std
41.28 0.84
41.38 0.02
41.28 0.02
41.18 0.03
41.45 0.07
R1
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
R2
2.20
2.16
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.14
2.12
Step II
Case B
R3
ave+/-std
R1
35.79 0.06 1.80
37.99 0.07 1.80
[-2.18] 39.15 0.08 1.80
-1.87
39.25 0.27 1.80
-1.57
39.50 0.21 1.80
-1.26
39.96 0.20 1.80
-0.96
40.75 0.25 1.80
-0.80
41.34 0.23 1.80
-0.65
41.99 0.22 1.80
-0.50
42.62 0.20 1.80
-0.34
43.19 0.19 1.80
-0.19
43.68 0.21 1.80
-0.04
43.92 0.25 1.80
0.11
43.98 0.26 1.80
0.27
43.86 0.24 1.80
0.42
43.67 0.21 1.80
0.57
43.45 0.20 1.80
0.73
43.09 0.20 1.80
0.88
42.67 0.19 1.80
1.19
42.03 0.15 1.80
1.49
41.60 0.18 1.80
[1.80]
41.47 0.20 1.80
41.55 0.04 1.80
S15
R2
2.20
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.14
2.12
Case C
R3
ave+/-std
35.79 0.06
[-2.18] 37.99 0.07
-1.87
38.12 0.20
-1.57
38.37 0.20
-1.26
38.61 0.19
-1.11
38.86 0.18
-0.96
39.31 0.17
-0.80
39.88 0.18
-0.65
40.44 0.18
-0.50
40.92 0.14
-0.34
41.35 0.12
-0.19
41.73 0.09
-0.04
42.09 0.09
0.11
42.25 0.13
0.27
42.24 0.16
0.42
42.04 0.23
0.57
41.70 0.27
0.73
41.30 0.29
1.03
40.56 0.25
1.34
40.17 0.26
[1.65]
40.07 0.29
40.30 0.04
40.38 0.04
R1
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
R2
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.16
2.14
2.12
Case D
R3
[-2.33]
-2.03
-1.72
-1.42
-1.26
-1.11
-0.96
-0.80
-0.65
-0.50
-0.34
-0.19
-0.04
0.11
0.27
0.42
0.57
0.88
1.19
[1.49]
ave+/-std
35.79 0.06
35.85 0.30
36.07 0.28
36.53 0.29
36.82 0.30
37.21 0.31
37.74 0.30
38.32 0.23
38.98 0.22
39.69 0.25
40.33 0.26
40.99 0.25
41.38 0.28
41.75 0.23
42.01 0.21
42.13 0.22
42.08 0.21
41.73 0.16
41.40 0.20
41.27 0.21
42.20 0.07
42.43 0.04
42.52 0.04
index
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
R1
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.88
1.92
1.96
2.00
2.00
R2
2.00
1.96
1.92
1.88
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.80
77
78
79
80
81
82
R1
2.00
2.04
2.08
2.12
2.16
2.18
R2
1.80
1.80
1.80
1.80
1.80
1.80
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
R1
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.18
2.20
2.22
2.25
R2
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
R1
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.70
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
3.70
R2
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.76
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
1.72
Step
Case A
R3
ave+/-std
41.45 0.05
41.16 0.01
41.13 0.01
41.19 0.02
[-6.94] 41.37 0.03
-5.86
42.42 0.56
-4.77
44.74 0.33
-3.69
47.64 0.28
-3.15
48.65 0.31
-2.61
49.27 0.29
-2.07
49.70 0.23
-1.53
49.94 0.18
-0.99
50.09 0.15
-0.45
50.07 0.20
0.09
50.15 0.25
0.63
50.07 0.19
1.17
49.92 0.17
1.71
49.74 0.19
2.25
49.37 0.18
2.79
48.77 0.25
3.33
47.90 0.29
4.41
45.65 0.35
5.50
43.48 0.49
[6.40]
42.67 0.58
42.39 0.06
42.30 0.06
42.23 0.02
42.20 0.06
41.85 0.09
Step V
R3
ave+/-std
42.46 0.61
42.39 0.02
42.29 0.07
42.13 0.09
41.80 0.10
41.68 0.11
Case A
R3
[1.89]
1.55
1.22
1.05
0.88
0.71
0.55
0.38
0.21
0.04
-0.13
-0.29
-0.46
-0.63
-0.80
-0.97
-1.13
-1.30
-1.64
[-1.97]
ave+/-std
41.68 0.11
41.78 0.32
42.14 0.27
42.40 0.27
42.72 0.27
43.06 0.24
43.33 0.25
43.48 0.25
43.56 0.21
43.48 0.22
43.13 0.20
42.55 0.21
41.89 0.19
41.12 0.21
40.45 0.21
39.85 0.22
39.26 0.24
38.83 0.21
38.33 0.26
38.17 0.25
37.09 0.17
36.04 0.14
34.54 0.11
IV
R1
1.84
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.92
1.96
2.00
R1
2.18
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.22
2.25
R2
2.00
2.00
1.96
1.92
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.88
1.84
1.80
1.80
1.80
1.80
Case B
R3
ave+/-std
41.45 0.07
42.09 0.08
41.82 0.04
41.68 0.03
[-7.12] 41.65 0.08
-6.04
42.57 0.84
-4.96
44.83 0.75
-3.87
47.99 0.51
-2.79
50.02 0.40
-2.25
50.84 0.36
-1.71
51.60 0.36
-1.17
52.26 0.43
-0.63
52.67 0.46
-0.09
52.89 0.51
0.45
52.97 0.49
0.99
52.80 0.55
1.53
52.71 0.61
2.07
52.45 0.58
2.61
51.90 0.57
3.15
51.13 0.60
3.69
49.90 0.59
4.23
48.21 0.50
5.32
45.46 0.42
[6.40]
44.22 0.49
43.84 0.12
43.72 0.12
43.41 0.09
43.17 0.05
43.07 0.04
R2
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
Step
Case B
R3
ave+/-std
41.68 0.11
[1.55]
41.52 0.11
1.22
41.83 0.19
1.05
42.10 0.19
0.88
42.32 0.20
0.71
42.51 0.20
0.55
42.60 0.24
0.38
42.58 0.29
0.21
42.56 0.31
0.04
42.38 0.32
-0.13
41.96 0.33
-0.29
41.36 0.37
-0.46
40.65 0.38
-0.63
39.84 0.37
-0.80
39.08 0.38
-0.97
38.52 0.38
-1.13
38.13 0.35
-1.30
37.79 0.33
-1.47
37.52 0.32
-1.64
37.33 0.32
[-1.81] 37.28 0.32
36.23 0.14
34.73 0.11
Step VII
R3
ave+/-std
34.72 0.38
32.34 0.09
30.18 0.09
28.09 0.08
26.06 0.05
24.13 0.03
22.21 0.06
20.19 0.07
18.28 0.08
16.71 0.12
15.91 0.14
15.53 0.14
12.00 0.10
8.99
0.11
6.40
0.11
4.34
0.12
2.70
0.12
1.30
0.16
0.23
0.20
-0.65 0.20
-1.16 0.14
-1.69 0.12
S16
VI
R1
2.18
2.20
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.22
2.25
R2
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
Case C
R3
ave+/-std
41.68 0.11
41.52 0.11
[1.55]
41.31 0.10
1.22
41.58 0.18
1.05
41.75 0.20
0.88
41.91 0.22
0.71
42.22 0.21
0.55
42.51 0.19
0.38
42.59 0.21
0.21
42.38 0.22
0.04
42.06 0.22
-0.13
41.50 0.19
-0.29
40.73 0.22
-0.46
39.87 0.28
-0.63
39.22 0.34
-0.80
38.54 0.33
-0.97
37.72 0.34
-1.13
37.02 0.35
-1.30
36.54 0.28
-1.47
36.21 0.23
-1.64
35.97 0.25
[-1.97] 35.78 0.29
34.28 0.11
R1
2.18
2.20
2.22
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
R2
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
1.80
Case D
R3
ave+/-std
41.68 0.11
41.52 0.11
41.31 0.10
[1.55]
40.86 0.14
1.22
41.13 0.18
1.05
41.30 0.20
0.88
41.46 0.22
0.71
41.77 0.21
0.55
42.06 0.19
0.38
42.15 0.21
0.21
41.93 0.22
0.04
41.61 0.22
-0.13
41.05 0.19
-0.29
40.28 0.22
-0.46
39.42 0.28
-0.63
38.78 0.34
-0.80
38.10 0.33
-0.97
37.27 0.34
-1.13
36.57 0.35
-1.30
36.09 0.28
-1.47
35.76 0.23
-1.64
35.52 0.25
[-1.97] 35.33 0.29
Table S2: The lateral SN 2 paths and the free energy. The table shows the data in Fig. 5.
The points in the lateral SN 2 path, their index and their free energies are listed. If the column in
R3 is blank, the simulation is done by constraining only R1 and R2. R3 represents Y in step 2.
Coordinates R1, R2 and Y are explained in the main text. If the value of R3 is in ”[]”, it means
that the two points, one with two coordinates and the other with three coordinates overlap. In step
II, the free energy of the end point is averaged over the four results, to give 55.37±0.91 kcal/mol.
The free energy is in units of kcal/mol. The simulation is divided into ten parts, over which
ten free energy landscapes are estimated and the average and standard deviation are then evaluated.
Index
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
R1
1.68
1.68
1.68
1.68
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
R2
3.60
3.50
3.40
3.30
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.10
3.00
2.90
2.80
2.70
2.60
2.55
2.50
2.45
2.40
2.35
2.30
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
Case
R1
2.30
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.30
A
R2
2.30
2.30
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
Step I
R3
ave+/-std
0.00
0.16
0.66
0.18
1.37
0.14
2.25
0.06
3.49
0.08
3.54
0.07
4.23
0.08
5.26
0.08
6.63
0.06
8.35
0.06
10.26 0.06
12.33 0.05
14.44 0.05
16.54 0.06
18.73 0.06
20.90 0.07
22.88 0.08
24.87 0.08
27.36 0.07
29.69 0.04
31.30 0.05
33.02 0.05
35.34 0.05
38.44 0.05
41.85 0.06
45.84 0.07
47.92 0.07
50.01 0.07
52.12 0.08
54.15 0.08
56.32 0.11
58.00 0.12
R3
[-1.05]
-0.89
-0.72
-0.56
-0.40
-0.24
-0.08
0.08
0.24
0.40
0.56
0.72
1.05
[1.21]
ave+/-std
58.00 0.12
57.16 0.17
60.24 0.12
60.30 0.42
60.44 0.38
60.61 0.39
60.76 0.43
60.85 0.45
60.89 0.50
60.91 0.59
60.77 0.59
60.54 0.50
60.33 0.43
60.17 0.39
59.94 0.37
59.89 0.36
55.22 0.10
Case
R1
2.30
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.30
B
R2
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.20
2.20
R3
[-1.37]
-1.21
-1.05
-0.89
-0.72
-0.56
-0.40
-0.24
-0.08
0.08
0.24
0.40
0.56
[0.72]
Step II
Case
ave+/-std
R1
58.00 0.12 2.30
57.16 0.17 2.20
57.19 0.53 2.20
57.35 0.51 2.30
57.64 0.49 2.30
58.06 0.46 2.30
58.58 0.44 2.30
59.22 0.43 2.30
59.93 0.44 2.30
60.57 0.47 2.30
61.05 0.49 2.30
61.48 0.47 2.30
61.74 0.42 2.30
61.75 0.36 2.30
61.69 0.34 2.30
60.34 0.04 2.30
55.66 0.10 2.30
S17
C
R2
2.30
2.30
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
2.20
R3
[-0.56]
-0.40
-0.24
-0.08
0.08
0.24
0.40
0.56
0.72
0.89
1.05
1.21
1.37
[1.53]
ave+/-std
58.00 0.12
57.16 0.17
60.24 0.12
58.86 0.24
58.64 0.17
58.35 0.22
57.98 0.24
57.56 0.28
57.07 0.30
56.48 0.31
55.81 0.29
55.18 0.25
54.69 0.20
54.36 0.15
54.16 0.17
54.05 0.23
54.04 0.29
Case
R1
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.20
2.20
2.30
D
R2
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.20
2.20
R3
[-1.05]
-0.89
-0.72
-0.56
-0.40
-0.24
-0.08
0.08
0.24
0.40
0.56
0.72
0.89
[1.05]
ave+/-std
58.00 0.12
58.06 0.57
58.22 0.54
58.48 0.50
58.83 0.46
59.24 0.45
59.52 0.47
59.59 0.44
59.58 0.40
59.55 0.41
59.47 0.42
59.37 0.43
59.28 0.44
59.24 0.46
62.58 0.08
61.24 0.04
56.56 0.10
Index
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
R1
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.30
3.30
3.40
3.50
3.60
3.70
R2
2.20
2.16
2.12
2.08
2.04
2.00
1.96
1.92
1.88
1.84
1.80
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.72
1.68
1.68
1.68
1.68
1.68
Step III
R3 ave+/-std
55.37 0.91
54.00 0.04
52.46 0.05
50.87 0.03
49.06 0.04
47.18 0.04
45.25 0.04
43.32 0.05
41.61 0.04
40.02 0.05
38.59 0.04
37.50 0.07
34.91 0.07
32.18 0.06
29.29 0.06
26.48 0.08
23.89 0.06
21.58 0.06
17.28 0.10
13.55 0.12
10.63 0.18
8.37
0.14
6.54
0.05
5.09
0.06
4.06
0.04
2.98
0.06
2.58
0.10
1.78
0.11
1.15
0.11
0.89
0.12
0.74
0.10
S18
Table S3: The integral route to obtain the starting structures of the points on
a rectangular grid. The columns of ”Fig. 2A”, ”Fig. 2B”, ”Fig. 2C”, ”Fig. 2D”,
”Fig. 2E” and ”Fig. 2F” correspond to the FES’s in Fig. 2A, Fig. 2B, Fig. 2C, Fig.
2D, Fig. 2E and Fig. 2F, respectively. We start from the initial structure and first follow
”first-coordinate path” to generate a row/column of structures, and then follow the ”secondcoordinate paths” to generate all of the other structures. Here we just show one of the
paths in the ”second-coordinate paths”. For instance, in ”Fig. 2A”, R2=3.6 Å is just one
example. It can be any value of R2 listed in ”first-coordinate”. All values are in units of Å.
Fig. 2A
Fig. 2B
Initial structure
R1
R2
R1
R2
1.80 3.60 1.80 3.60
first-coordinate path
Forward
Forward
R1
R2
R1
R2
1.80 3.60 1.80 3.60
1.80 3.50 1.84 3.60
1.80 3.40 1.88 3.60
1.80 3.30 1.92 3.60
1.80 3.20 1.96 3.60
1.80 3.10 2.00 3.60
1.80 3.00 2.04 3.60
1.80 2.90 2.08 3.60
1.80 2.80 2.12 3.60
1.80 2.70 2.16 3.60
1.80 2.65 2.20 3.60
1.80 2.60 2.25 3.60
1.80 2.55 2.30 3.60
1.80 2.50 2.35 3.60
1.80 2.45 2.40 3.60
1.80 2.40 2.45 3.60
1.80 2.35 2.50 3.60
1.80 2.30 2.55 3.60
1.80 2.25 2.60 3.60
1.80 2.20 2.65 3.60
1.80 2.16 2.70 3.60
1.80 2.12 2.80 3.60
1.80 2.08 2.90 3.60
1.80 2.04 3.00 3.60
1.80 2.00 3.10 3.60
1.80 1.96 3.20 3.60
1.80 1.92 3.30 3.60
1.80 1.88 3.40 3.60
1.80 1.84 3.50 3.60
1.80 1.80 3.60 3.60
1.80 1.76 3.70 3.60
1.80 1.72 Backward
1.80 1.68 R1
R2
1.80 1.66 1.76 3.60
1.80 1.64 1.72 3.60
1.68 3.60
1.64 3.60
Fig. 2C
Fig. 2D
Fig. 2E
Fig. 2F
R1
1.80
R1
1.64
R1
3.30
R1
3.30
R2
1.64
Forward
R1
R2
1.80 1.64
1.80 1.66
1.80 1.68
1.80 1.72
1.80 1.76
1.80 1.80
1.80 1.84
1.80 1.88
1.80 1.92
1.80 1.96
1.80 2.00
1.80 2.04
1.80 2.08
1.80 2.12
1.80 2.16
1.80 2.20
1.80 2.25
1.80 2.30
1.80 2.35
1.80 2.40
1.80 2.45
1.80 2.50
1.80 2.55
1.80 2.60
1.80 2.65
1.80 2.70
1.80 2.80
1.80 2.90
1.80 3.00
1.80 3.10
1.80 3.20
1.80 3.30
1.80 3.40
1.80 3.50
1.80 3.60
R2
1.80
Forward
R1
R2
1.64 1.80
1.68 1.80
1.72 1.80
1.76 1.80
1.80 1.80
1.84 1.80
1.88 1.80
1.92 1.80
1.96 1.80
2.00 1.80
2.04 1.80
2.08 1.80
2.12 1.80
2.16 1.80
2.20 1.80
2.25 1.80
2.30 1.80
2.35 1.80
2.40 1.80
2.45 1.80
2.50 1.80
2.55 1.80
2.60 1.80
2.65 1.80
2.70 1.80
2.80 1.80
2.90 1.80
3.00 1.80
3.10 1.80
3.20 1.80
3.30 1.80
3.40 1.80
3.50 1.80
3.60 1.80
3.70 1.80
R2
1.80
Forward
R1
R2
3.30 1.80
3.20 1.80
3.10 1.80
3.00 1.80
2.90 1.80
2.80 1.80
2.70 1.80
2.65 1.80
2.60 1.80
2.55 1.80
2.50 1.80
2.45 1.80
2.40 1.80
2.35 1.80
2.30 1.80
2.25 1.80
2.20 1.80
2.16 1.80
2.12 1.80
2.08 1.80
2.04 1.80
2.00 1.80
1.96 1.80
1.92 1.80
1.88 1.80
1.84 1.80
1.80 1.80
1.76 1.80
1.72 1.80
1.68 1.80
1.64 1.80
Backward
R1
R2
3.40 1.80
3.50 1.80
3.60 1.80
3.70 1.80
R2
1.80
Forward
R1
R2
3.30 1.80
3.30 1.84
3.30 1.88
3.30 1.92
3.30 1.96
3.30 2.00
3.30 2.04
3.30 2.08
3.30 2.12
3.30 2.16
3.30 2.20
3.30 2.25
3.30 2.30
3.30 2.35
3.30 2.40
3.30 2.45
3.30 2.50
3.30 2.55
3.30 2.60
3.30 2.65
3.30 2.70
3.30 2.80
3.30 2.90
3.30 3.00
3.30 3.10
3.30 3.20
3.30 3.30
3.30 3.40
3.30 3.50
3.30 3.60
Backward
R1
R2
3.30 1.76
3.30 1.72
3.30 1.68
3.30 1.66
3.30 1.64
Fig. 2A
Fig. 2B
second-coordinate paths
Forward
Forward
R1
R2
R1
R2
1.84 3.60 1.80 3.50
1.88 3.60 1.80 3.40
1.92 3.60 1.80 3.30
1.96 3.60 1.80 3.20
2.00 3.60 1.80 3.10
2.04 3.60 1.80 3.00
2.08 3.60 1.80 2.90
2.12 3.60 1.80 2.80
2.16 3.60 1.80 2.70
2.20 3.60 1.80 2.65
2.25 3.60 1.80 2.60
2.30 3.60 1.80 2.55
2.35 3.60 1.80 2.50
2.40 3.60 1.80 2.45
2.45 3.60 1.80 2.40
2.50 3.60 1.80 2.35
2.55 3.60 1.80 2.30
2.60 3.60 1.80 2.25
2.65 3.60 1.80 2.20
2.70 3.60 1.80 2.16
2.80 3.60 1.80 2.12
2.90 3.60 1.80 2.08
3.00 3.60 1.80 2.04
3.10 3.60 1.80 2.00
3.20 3.60 1.80 1.96
3.30 3.60 1.80 1.92
3.40 3.60 1.80 1.88
3.50 3.60 1.80 1.84
3.60 3.60 1.80 1.80
3.70 3.60 1.80 1.76
Backward
1.80 1.72
R1
R2
1.80 1.68
1.76 3.60 1.80 1.66
1.72 3.60 1.80 1.64
1.68 3.60
1.64 3.60
S19
Fig. 2C
Fig. 2D
Fig. 2E
Fig. 2F
Forward
R1
R2
1.84 1.64
1.88 1.64
1.92 1.64
1.96 1.64
2.00 1.64
2.04 1.64
2.08 1.64
2.12 1.64
2.16 1.64
2.20 1.64
2.25 1.64
2.30 1.64
2.35 1.64
2.40 1.64
2.45 1.64
2.50 1.64
2.55 1.64
2.60 1.64
2.65 1.64
2.70 1.64
2.80 1.64
2.90 1.64
3.00 1.64
3.10 1.64
3.20 1.64
3.30 1.64
3.40 1.64
3.50 1.64
3.60 1.64
3.70 1.64
Backward
R1
R2
1.76 1.64
1.72 1.64
1.68 1.64
1.64 1.64
Forward
R1
R2
1.80 1.84
1.80 1.88
1.80 1.92
1.80 1.96
1.80 2.00
1.80 2.04
1.80 2.08
1.80 2.12
1.80 2.16
1.80 2.20
1.80 2.25
1.80 2.30
1.80 2.35
1.80 2.40
1.80 2.45
1.80 2.50
1.80 2.55
1.80 2.60
1.80 2.65
1.80 2.70
1.80 2.80
1.80 2.90
1.80 3.00
1.80 3.10
1.80 3.20
1.80 3.30
1.80 3.40
1.80 3.50
1.80 3.60
Backward
R1
R2
1.80 1.76
1.80 1.72
1.80 1.68
1.80 1.66
1.80 1.64
Forward
R1
R2
3.30 1.84
3.30 1.88
3.30 1.92
3.30 1.96
3.30 2.00
3.30 2.04
3.30 2.08
3.30 2.12
3.30 2.16
3.30 2.20
3.30 2.25
3.30 2.30
3.30 2.35
3.30 2.40
3.30 2.45
3.30 2.50
3.30 2.55
3.30 2.60
3.30 2.65
3.30 2.70
3.30 2.80
3.30 2.90
3.30 3.00
3.30 3.10
3.30 3.20
3.30 3.30
3.30 3.40
3.30 3.50
3.30 3.60
Backward
R1
R2
3.30 1.76
3.30 1.72
3.30 1.68
3.30 1.66
3.30 1.64
Forward
R1
R2
3.20 1.80
3.10 1.80
3.00 1.80
2.90 1.80
2.80 1.80
2.70 1.80
2.65 1.80
2.60 1.80
2.55 1.80
2.50 1.80
2.45 1.80
2.40 1.80
2.35 1.80
2.30 1.80
2.25 1.80
2.20 1.80
2.16 1.80
2.12 1.80
2.08 1.80
2.04 1.80
2.00 1.80
1.96 1.80
1.92 1.80
1.88 1.80
1.84 1.80
1.80 1.80
1.76 1.80
1.72 1.80
1.68 1.80
1.64 1.80
Backward
R1
R2
3.40 1.80
3.50 1.80
3.60 1.80
3.70 1.80
Table S4: The free energy data of the six FES’s shown in Fig. 2. Cases A, B,
C, D, E and F correspond to the FES’s in Fig. 2A, Fig. 2B, Fig. 2C, Fig. 2D, Fig. 2E
and Fig. 2F, respectively. The simulation is divided into ten parts, over which ten free energies are estimated for each point and the average and standard deviation are then evaluated.
Points
R1
R2
1.64 1.64
1.64 1.66
1.64 1.68
1.64 1.72
1.64 1.76
1.64 1.80
1.64 1.84
1.64 1.88
1.64 1.92
1.64 1.96
1.64 2.00
1.64 2.04
1.64 2.08
1.64 2.12
1.64 2.16
1.64 2.20
1.64 2.25
1.64 2.30
1.64 2.35
1.64 2.40
1.64 2.45
1.64 2.50
1.64 2.55
1.64 2.60
1.64 2.65
1.64 2.70
1.64 2.80
1.64 2.90
1.64 3.00
1.64 3.10
1.64 3.20
1.64 3.30
1.64 3.40
1.64 3.50
1.64 3.60
Free energy
Case A
59.0 0.3
57.3 0.4
56.1 0.3
53.7 0.2
51.8 0.3
50.1 0.3
49.0 0.2
47.8 0.3
47.5 0.2
47.2 0.2
46.7 0.3
45.4 0.2
45.8 0.2
45.3 0.3
44.1 0.2
40.8 0.2
38.5 0.2
35.4 0.2
32.7 0.2
29.9 0.3
26.5 0.3
23.9 0.2
21.6 0.2
19.0 0.2
16.8 0.3
15.4 0.3
11.6 0.3
9.4
0.2
7.3
0.3
6.1
0.4
4.3
0.4
3.0
0.5
2.1
0.4
0.7
0.5
0.7
0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
66.2 0.8 54.8 0.6 52.0
64.4 0.8 53.1 0.3 50.4
62.8 0.8 50.9 0.4 48.9
60.2 0.8 49.2 0.5 46.9
58.1 0.8 46.9 0.4 45.3
56.5 0.8 45.4 0.3 44.4
55.5 0.8 44.4 0.3 43.5
54.6 0.9 43.6 0.3 42.8
53.9 0.9 43.0 0.4 42.8
53.3 0.9 43.2 0.2 43.0
52.8 0.9 42.8 0.3 43.1
52.2 0.9 41.6 0.2 43.3
51.5 0.9 41.6 0.2 43.7
49.9 0.9 40.9 0.3 44.3
47.0 0.9 40.6 0.3 44.8
44.2 0.8 40.5 0.3 45.2
41.0 0.8 36.3 0.2 45.5
38.1 0.8 33.5 0.2 45.7
34.9 0.8 31.3 0.3 45.7
31.7 0.7 27.4 0.3 45.5
28.8 0.7 25.4 0.2 45.1
26.1 0.7 23.0 0.4 43.8
23.4 0.7 20.0 0.3 42.5
21.2 0.7 17.3 0.4 41.9
19.0 0.7 15.8 0.3 40.3
17.0 0.7 13.7 0.4 38.7
13.5 0.7 10.5 0.4 36.8
10.4 0.6 7.9
0.3 33.8
8.1
0.6 4.5
0.3 31.9
6.2
0.5 3.6
0.3 31.0
4.1
0.5 2.4
0.3 30.6
2.8
0.4 1.9
0.3 30.0
2.1
0.3 0.7
0.5 28.5
1.7
0.2 0.8
0.8 27.4
1.2
0.2 1.4
0.7 26.9
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
56.1
54.5
53.0
51.0
49.1
47.3
46.4
45.4
45.1
45.0
44.5
43.7
43.8
43.5
42.0
39.3
36.8
33.9
31.2
28.7
25.4
22.6
20.3
17.9
15.6
14.3
10.6
8.3
6.3
5.0
3.3
2.3
1.1
0.0
0.0
58.7
56.9
55.4
53.0
51.0
49.6
48.6
47.7
46.9
46.3
45.9
45.5
45.2
44.0
42.0
39.7
36.7
33.7
30.6
27.5
24.8
22.4
20.0
17.4
15.2
13.3
9.5
7.3
5.8
4.1
2.7
1.7
0.9
0.3
0.0
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.2
0.3
0.3
0.2
0.3
0.2
0.2
0.3
0.2
0.2
0.3
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.2
0.2
0.2
0.3
0.3
0.2
0.2
0.3
0.4
0.4
0.5
0.4
0.6
0.6
1.4
1.4
1.4
1.4
1.4
1.4
1.4
1.5
1.4
1.4
1.4
1.4
1.4
1.2
1.0
0.9
0.9
0.9
1.0
1.0
0.9
0.9
1.0
1.0
1.0
1.0
0.8
0.7
0.6
0.5
0.4
0.3
0.3
0.3
0.2
51.8
50.1
48.2
46.3
44.2
42.7
41.7
41.1
40.8
40.8
40.5
39.6
39.8
39.1
38.9
38.5
34.5
31.9
29.5
26.1
23.9
21.8
18.7
16.2
14.8
12.6
9.6
7.1
4.1
2.8
1.6
1.0
-0.1
0.0
0.6
0.6
0.4
0.5
0.4
0.4
0.3
0.3
0.3
0.4
0.2
0.2
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.4
0.3
0.2
0.4
0.3
0.3
0.3
0.4
0.4
0.3
0.3
0.3
0.3
0.4
0.5
0.8
0.7
48.1
46.6
45.4
43.6
42.4
41.6
41.1
40.9
40.9
41.2
41.5
41.9
42.5
42.6
42.7
43.1
43.5
43.6
43.5
43.0
42.6
42.3
41.1
39.7
38.8
37.4
34.1
31.4
28.4
26.5
25.0
23.1
21.7
20.2
19.1
D
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.6
0.6
0.6
0.7
0.7
0.8
0.8
0.8
0.9
0.9
0.9
1.0
Case
70.8
69.1
67.7
65.6
64.2
63.2
62.9
62.7
62.8
63.0
63.0
63.3
63.6
63.9
64.1
64.3
64.2
63.8
63.7
63.6
63.4
63.1
62.4
61.1
59.8
58.4
55.1
53.0
50.5
48.0
46.7
46.7
45.9
44.2
43.4
E
0.9
0.9
0.9
0.8
0.8
0.9
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.6
0.7
0.9
0.8
0.8
0.8
0.8
0.8
0.9
1.0
1.0
1.2
1.1
1.0
1.1
1.0
0.9
1.0
1.1
1.1
Case
65.8
59.8
59.9
89.6
64.2
77.9
57.6
76.4
84.5
83.4
87.7
90.0
91.0
85.6
79.3
88.2
88.8
88.6
87.9
87.1
86.5
85.7
84.9
84.3
83.2
79.7
81.6
77.5
68.2
66.1
74.1
67.1
72.8
62.5
65.4
F
1.4
0.8
0.7
0.7
0.8
1.3
0.7
1.0
0.8
0.6
0.6
0.8
0.7
0.7
0.9
0.3
0.5
0.7
0.7
0.6
0.8
0.7
0.5
0.4
0.6
0.7
0.5
0.5
0.7
0.7
0.4
0.8
0.7
0.8
0.6
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.4
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.8
0.9
1.0
1.0
0.9
0.9
1.2
1.3
67.4
65.9
64.7
62.6
61.2
60.3
60.0
59.7
59.7
60.0
60.4
60.8
61.1
61.4
61.7
62.3
62.7
62.5
62.6
62.5
62.4
62.1
61.9
60.4
58.7
58.1
55.7
53.3
51.3
49.1
47.4
46.2
44.5
43.2
42.4
0.9
0.9
0.9
0.9
0.9
0.8
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.8
0.8
0.8
0.8
0.7
0.7
0.6
0.7
0.6
0.6
0.7
0.8
0.8
60.5
56.7
56.6
83.1
61.1
75.1
54.6
71.6
78.3
77.4
81.7
84.2
85.2
80.1
74.6
82.6
83.2
82.8
82.3
76.8
81.3
82.4
76.0
79.3
78.4
74.6
76.8
73.1
70.8
71.6
71.9
68.5
63.4
60.2
61.8
1.1
0.8
0.7
0.7
0.8
1.3
0.7
0.7
0.8
0.5
0.6
0.8
0.7
0.8
0.7
0.4
0.5
0.7
0.6
0.4
0.7
0.6
0.5
0.4
0.7
0.7
0.5
0.5
0.9
0.8
0.4
0.5
0.6
0.6
0.6
Points
R1
R2
2.40 1.64
2.40 1.66
2.40 1.68
2.40 1.72
2.40 1.76
2.40 1.80
2.40 1.84
2.40 1.88
2.40 1.92
2.40 1.96
2.40 2.00
2.40 2.04
2.40 2.08
2.40 2.12
2.40 2.16
2.40 2.20
2.40 2.25
2.40 2.30
2.40 2.35
2.40 2.40
2.40 2.45
2.40 2.50
2.40 2.55
2.40 2.60
2.40 2.65
2.40 2.70
2.40 2.80
2.40 2.90
2.40 3.00
2.40 3.10
2.40 3.20
2.40 3.30
2.40 3.40
2.40 3.50
2.40 3.60
Free energy
Case A
52.1 0.3
50.7 0.5
50.8 0.6
47.1 0.4
47.8 0.5
48.0 0.5
47.1 0.4
52.1 0.4
52.2 0.3
54.3 0.3
56.1 0.3
55.7 0.3
59.4 0.3
58.1 0.3
56.8 0.2
52.3 0.4
50.3 0.4
49.2 0.2
48.5 0.3
47.5 0.3
46.3 0.3
44.0 0.3
41.7 0.5
39.2 0.3
40.6 0.6
39.1 0.5
37.5 0.4
32.5 0.2
33.0 0.4
30.3 0.5
29.8 0.5
31.6 0.4
30.3 0.4
28.4 0.5
28.8 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
84.4 0.5 46.5 0.4 29.9
81.3 0.5 43.1 0.5 28.9
79.7 0.5 44.2 0.4 28.1
77.7 0.5 45.7 0.3 27.5
73.2 0.5 42.7 0.3 27.5
70.0 0.5 43.3 0.3 28.1
67.1 0.6 45.3 0.3 29.1
64.7 0.6 46.0 0.4 30.3
62.5 0.6 47.7 0.5 31.5
60.6 0.6 47.0 0.4 32.9
58.8 0.6 51.2 0.2 34.4
57.1 0.6 52.9 0.2 35.8
55.6 0.6 54.7 0.4 37.1
54.2 0.6 55.6 0.4 38.1
52.9 0.6 55.2 0.3 39.1
51.3 0.6 50.0 0.3 40.2
49.7 0.5 48.8 0.3 41.7
48.3 0.5 48.1 0.3 42.7
46.7 0.5 46.4 0.4 43.6
45.5 0.5 44.0 0.2 44.5
44.5 0.5 46.2 0.3 45.1
43.4 0.5 44.2 0.5 45.7
42.3 0.6 41.1 0.4 46.2
41.2 0.5 39.3 0.4 46.5
40.0 0.5 39.1 0.4 46.8
38.6 0.6 38.3 0.3 46.7
36.2 0.6 36.4 0.4 46.4
34.5 0.5 33.9 0.4 45.5
33.4 0.5 33.6 0.4 44.7
32.5 0.5 33.8 0.5 43.8
31.4 0.4 32.9 0.5 42.9
30.6 0.4 31.1 0.5 42.1
30.2 0.3 32.5 0.6 41.2
30.1 0.3 32.1 0.8 40.7
30.2 0.2 31.7 0.7 40.5
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
50.8
50.5
50.7
45.6
47.5
46.9
47.3
52.6
52.5
54.6
56.4
56.5
60.1
59.1
57.5
52.9
51.0
49.9
49.2
48.6
47.4
44.9
43.1
40.4
42.0
40.7
39.0
34.0
34.5
31.9
31.6
33.4
32.1
30.1
30.5
84.2
81.4
78.8
74.4
70.2
69.1
68.4
65.6
63.5
61.5
59.9
58.3
56.7
55.4
54.2
53.0
51.8
50.4
49.2
48.1
46.7
45.4
44.2
43.3
42.5
41.5
39.8
38.5
37.1
35.6
34.5
33.6
32.9
32.6
32.3
S20
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.5
0.6
0.6
0.5
0.6
0.6
0.4
0.3
0.3
0.4
0.3
0.3
0.3
0.2
0.4
0.4
0.2
0.3
0.3
0.3
0.2
0.5
0.3
0.6
0.5
0.4
0.2
0.4
0.5
0.6
0.3
0.4
0.5
0.6
1.0
1.0
0.9
0.9
0.9
0.9
1.0
0.9
0.9
0.9
1.0
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.8
0.7
0.5
0.4
0.5
0.4
0.3
0.2
45.7
43.3
43.9
45.3
42.6
41.9
45.7
46.1
47.6
46.5
51.7
53.8
55.4
56.4
56.2
50.6
49.3
48.8
47.3
45.2
47.4
45.6
42.4
40.9
40.3
40.0
38.2
35.7
35.3
35.9
34.7
32.9
34.5
34.0
33.4
0.4
0.5
0.4
0.2
0.3
0.3
0.3
0.4
0.5
0.4
0.2
0.2
0.3
0.4
0.3
0.4
0.3
0.4
0.5
0.2
0.3
0.5
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.8
0.7
27.4
26.6
26.1
25.4
25.4
25.9
26.8
27.9
29.1
30.6
32.1
33.7
35.7
37.1
38.5
39.9
41.2
42.4
43.9
45.3
46.2
46.9
47.5
47.8
48.1
48.3
47.9
47.4
46.8
46.1
45.3
44.5
44.0
43.7
43.5
D
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.5
0.5
0.6
0.6
0.7
0.7
0.7
0.7
0.9
1.0
1.0
1.0
1.1
Case
30.7
29.7
28.9
28.7
29.1
29.7
30.3
31.3
32.6
33.9
35.4
37.1
38.6
39.9
41.2
42.5
44.1
45.7
47.1
48.1
48.7
49.5
50.1
50.3
50.1
49.9
49.1
48.0
47.2
46.5
45.4
44.4
43.8
43.1
42.8
E
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.4
0.5
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.8
0.7
0.7
Case
31.7
30.3
30.7
29.3
28.5
28.6
29.9
29.4
32.3
34.0
36.3
38.6
40.1
41.9
39.9
44.8
47.0
47.7
47.1
47.9
52.3
51.3
50.6
53.1
52.6
51.8
55.4
54.7
56.0
52.1
56.6
55.4
55.3
54.0
53.6
F
0.6
0.5
0.7
0.6
0.7
0.8
0.7
0.6
0.6
0.6
0.6
0.8
0.6
0.7
0.6
0.4
0.5
0.5
0.4
0.4
0.5
0.4
0.4
0.5
0.4
0.6
0.3
0.6
0.8
0.7
0.5
0.7
0.6
0.4
0.3
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.4
0.4
0.3
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.7
0.8
0.8
0.9
1.0
0.9
28.4
27.6
27.1
26.7
26.8
27.3
28.1
29.2
30.9
32.6
34.3
35.9
37.4
39.1
40.6
41.8
43.3
44.5
45.4
46.5
47.5
48.5
49.3
50.0
50.5
50.8
51.3
51.5
51.1
51.0
51.0
50.2
49.9
50.1
50.1
0.4
0.4
0.3
0.3
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.5
29.1
27.6
28.0
26.8
26.1
26.4
27.8
27.4
30.5
31.8
34.3
36.9
38.5
40.1
38.6
42.9
45.5
46.5
46.0
46.9
51.3
50.6
49.8
52.1
52.0
51.2
55.0
54.6
55.9
52.0
56.5
55.3
55.4
54.4
53.8
0.6
0.5
0.7
0.6
0.7
0.9
0.7
0.6
0.6
0.6
0.5
0.8
0.5
0.7
0.6
0.4
0.4
0.5
0.3
0.4
0.5
0.4
0.4
0.5
0.4
0.6
0.3
0.5
0.8
0.7
0.5
0.7
0.6
0.4
0.2
Points
R1
R2
1.72 1.64
1.72 1.66
1.72 1.68
1.72 1.72
1.72 1.76
1.72 1.80
1.72 1.84
1.72 1.88
1.72 1.92
1.72 1.96
1.72 2.00
1.72 2.04
1.72 2.08
1.72 2.12
1.72 2.16
1.72 2.20
1.72 2.25
1.72 2.30
1.72 2.35
1.72 2.40
1.72 2.45
1.72 2.50
1.72 2.55
1.72 2.60
1.72 2.65
1.72 2.70
1.72 2.80
1.72 2.90
1.72 3.00
1.72 3.10
1.72 3.20
1.72 3.30
1.72 3.40
1.72 3.50
1.72 3.60
Free energy
Case A
54.1 0.2
52.4 0.3
51.0 0.3
48.9 0.2
47.0 0.3
45.5 0.2
44.7 0.2
44.0 0.2
43.6 0.2
43.4 0.2
43.1 0.2
42.7 0.2
42.5 0.2
42.5 0.2
40.9 0.2
38.4 0.2
35.8 0.2
33.2 0.2
30.6 0.2
28.1 0.2
25.0 0.2
22.0 0.2
19.8 0.2
17.7 0.2
15.4 0.3
13.8 0.2
10.5 0.2
7.8
0.2
6.0
0.4
4.5
0.4
3.2
0.4
2.1
0.5
1.0
0.4
0.1
0.5
0.0
0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
57.8 0.6 49.7 0.5 46.3
56.1 0.6 47.9 0.4 44.8
54.6 0.7 46.2 0.5 43.5
52.0 0.6 44.2 0.4 41.5
50.2 0.6 42.3 0.3 40.1
48.8 0.6 40.9 0.3 39.5
47.7 0.6 40.0 0.3 39.4
47.0 0.6 39.5 0.3 39.4
46.5 0.7 39.3 0.4 39.7
46.3 0.7 39.2 0.2 40.1
46.0 0.7 39.0 0.2 40.8
45.8 0.7 38.4 0.2 41.4
44.3 0.7 38.7 0.2 41.9
41.6 0.7 38.2 0.2 42.6
39.3 0.7 37.9 0.2 43.3
37.0 0.7 37.4 0.2 43.7
34.1 0.6 33.5 0.2 44.1
31.1 0.6 30.9 0.2 44.1
28.6 0.6 28.7 0.3 44.0
26.3 0.7 25.6 0.3 44.0
24.2 0.7 23.3 0.2 43.8
22.1 0.6 21.3 0.3 42.2
20.2 0.6 18.2 0.3 39.4
18.2 0.6 15.8 0.3 37.0
16.5 0.5 14.4 0.3 34.7
14.6 0.6 12.1 0.4 32.7
11.1 0.6 9.3
0.4 29.3
8.4
0.6 6.8
0.3 26.7
5.7
0.6 4.4
0.3 25.3
3.8
0.5 2.8
0.3 23.7
2.3
0.4 1.6
0.2 22.6
1.2
0.4 1.1
0.4 22.6
0.5
0.4 0.0
0.5 22.8
0.0
0.2 0.0
0.8 23.0
-0.3 0.2 0.4
0.7 22.9
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
52.7
50.8
49.7
47.5
45.6
44.4
43.7
43.0
42.7
42.5
42.4
42.2
42.1
42.1
40.7
37.9
35.4
33.0
30.7
28.0
25.1
22.2
20.1
18.0
15.7
14.0
10.9
8.1
6.2
4.8
3.3
2.3
1.4
0.6
0.7
67.3
65.8
64.3
61.9
60.3
59.2
58.4
58.3
56.6
53.4
50.8
48.2
45.6
44.1
42.5
39.9
36.9
34.0
31.3
28.8
26.4
23.9
21.6
19.6
17.6
15.8
12.3
10.2
8.2
6.1
4.3
2.6
1.5
0.9
0.3
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.2
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.2
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.6
0.6
0.5
0.5
0.5
0.6
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.6
0.6
0.6
0.5
0.5
0.5
0.4
0.4
0.3
0.2
48.3
46.3
44.8
42.7
41.1
39.8
38.9
38.5
38.3
38.4
38.2
37.9
38.1
37.8
37.5
36.8
33.4
30.8
28.5
25.7
23.4
21.2
18.4
16.2
14.4
12.4
9.6
7.0
5.0
3.4
2.5
1.8
0.7
0.8
0.9
0.5
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.2
0.3
0.3
0.3
0.3
0.4
0.5
0.4
0.3
0.3
0.3
0.4
0.5
0.7
0.8
44.4
43.0
41.7
39.6
38.4
38.0
37.8
37.8
38.0
38.4
38.9
39.5
40.0
40.6
41.1
41.5
42.0
42.5
42.7
42.7
42.7
42.5
41.7
41.1
40.3
39.1
37.3
35.2
32.9
30.9
29.2
27.5
26.0
24.7
23.7
D
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.8
0.9
0.9
0.9
1.0
1.0
0.9
Case
64.5
63.0
61.7
59.8
58.5
57.9
57.6
57.3
57.4
57.8
58.4
59.1
59.7
60.5
60.9
61.2
61.7
62.0
62.2
62.4
62.4
62.2
60.7
58.1
56.7
56.2
54.6
52.6
50.9
50.1
49.5
49.2
48.5
47.5
47.4
E
0.9
0.9
0.8
0.8
0.8
0.8
0.9
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.9
0.9
0.9
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.0
0.9
0.9
0.9
0.8
0.8
Case
57.7
54.3
54.1
77.4
58.8
71.4
52.4
67.4
73.1
72.2
76.5
79.1
80.3
75.4
70.9
77.9
78.7
78.7
77.4
72.9
77.2
78.0
74.5
73.8
73.7
71.2
73.2
69.6
67.2
61.8
68.5
63.2
65.4
58.8
58.9
F
1.0
0.8
0.7
0.7
0.8
1.3
0.7
0.5
0.8
0.5
0.6
0.8
0.7
0.8
0.6
0.4
0.5
0.6
0.6
0.4
0.7
0.5
0.5
0.6
0.5
0.6
0.5
0.5
0.8
0.7
0.4
0.8
0.7
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.8
0.9
62.8
61.4
60.2
58.1
57.0
56.4
56.0
55.8
55.8
56.0
56.3
56.8
57.3
57.5
57.9
58.5
58.8
59.1
59.5
59.7
59.5
59.4
57.7
56.2
55.8
54.7
53.2
50.7
48.2
46.6
45.0
42.9
41.4
40.8
39.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.9
0.9
0.9
0.9
0.9
0.9
1.0
1.1
1.2
1.1
1.1
1.2
1.3
1.3
1.2
1.2
55.7
52.3
52.2
72.5
57.4
66.4
51.1
62.4
68.7
67.9
71.9
74.8
76.0
71.4
67.0
73.8
75.2
75.4
73.7
69.3
73.8
74.2
70.8
71.8
70.2
68.7
70.3
66.9
64.9
59.1
66.3
61.1
56.8
56.5
56.6
1.0
0.8
0.6
0.7
0.8
1.3
0.7
0.5
0.8
0.5
0.6
0.9
0.7
0.8
0.6
0.4
0.5
0.6
0.5
0.4
0.7
0.5
0.5
0.4
0.5
0.6
0.4
0.5
0.8
0.7
0.4
0.8
0.8
0.5
0.5
Points
R1
R2
2.50 1.64
2.50 1.66
2.50 1.68
2.50 1.72
2.50 1.76
2.50 1.80
2.50 1.84
2.50 1.88
2.50 1.92
2.50 1.96
2.50 2.00
2.50 2.04
2.50 2.08
2.50 2.12
2.50 2.16
2.50 2.20
2.50 2.25
2.50 2.30
2.50 2.35
2.50 2.40
2.50 2.45
2.50 2.50
2.50 2.55
2.50 2.60
2.50 2.65
2.50 2.70
2.50 2.80
2.50 2.90
2.50 3.00
2.50 3.10
2.50 3.20
2.50 3.30
2.50 3.40
2.50 3.50
2.50 3.60
Free energy
Case A
47.9 0.3
50.0 0.5
50.4 0.7
45.3 0.5
46.9 0.5
45.1 0.7
47.8 0.6
52.9 0.4
52.6 0.3
55.1 0.3
56.8 0.4
55.9 0.3
61.0 0.4
60.0 0.2
58.3 0.2
53.4 0.5
51.5 0.4
50.4 0.2
50.0 0.4
49.5 0.3
48.0 0.3
45.6 0.3
44.6 0.5
41.5 0.3
43.2 0.7
41.9 0.5
40.3 0.4
35.3 0.2
35.8 0.4
33.6 0.5
33.1 0.6
34.9 0.3
33.7 0.3
31.9 0.5
32.0 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
86.8 0.7 44.4 0.6 24.3
84.1 0.7 42.9 0.5 23.6
81.5 0.7 43.8 0.4 23.1
76.9 0.7 43.5 0.4 22.8
73.0 0.7 41.3 0.3 23.0
69.6 0.6 42.0 0.3 23.5
66.8 0.6 45.7 0.3 24.4
64.2 0.6 46.1 0.4 25.8
61.9 0.6 47.8 0.4 27.3
60.1 0.6 44.1 0.4 28.9
58.5 0.6 50.5 0.2 30.7
57.0 0.6 54.2 0.3 32.4
55.5 0.6 55.7 0.3 34.0
54.4 0.6 57.1 0.4 35.6
53.3 0.6 56.8 0.3 36.9
52.2 0.6 51.0 0.4 38.5
51.1 0.6 50.0 0.3 40.5
49.8 0.6 49.5 0.4 41.9
48.6 0.6 48.0 0.4 43.0
47.5 0.6 46.1 0.2 43.8
46.5 0.6 48.3 0.3 44.7
45.4 0.6 46.9 0.6 45.6
44.6 0.6 43.5 0.4 46.1
43.9 0.6 42.2 0.4 46.8
42.6 0.6 41.2 0.5 47.3
41.4 0.6 41.4 0.3 47.6
39.8 0.6 40.0 0.4 48.2
38.6 0.6 37.3 0.4 47.9
37.1 0.5 36.9 0.4 47.1
35.8 0.5 37.9 0.5 45.9
34.9 0.4 36.6 0.4 45.5
34.0 0.4 34.6 0.5 45.2
33.5 0.3 36.1 0.6 44.8
33.8 0.3 36.0 0.7 44.2
33.9 0.2 34.8 0.7 43.8
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
46.4
49.7
49.1
44.9
46.6
44.8
48.1
53.3
52.2
55.4
57.2
54.8
60.6
60.7
58.8
53.8
51.9
50.9
50.8
50.4
48.6
46.3
45.9
42.4
44.5
43.1
41.4
36.6
37.0
35.2
34.6
36.0
35.1
33.5
33.5
82.1
79.5
77.0
72.7
69.1
66.0
63.4
61.5
59.7
58.2
56.9
55.6
54.5
53.5
52.7
51.7
50.7
49.8
48.7
47.6
46.6
45.9
45.1
44.2
43.4
42.7
41.0
39.6
38.4
37.5
36.4
35.9
35.6
35.6
35.8
S21
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.5
0.6
0.6
0.5
0.7
0.6
0.4
0.3
0.4
0.4
0.3
0.4
0.2
0.2
0.5
0.4
0.1
0.4
0.4
0.3
0.3
0.6
0.4
0.7
0.4
0.4
0.3
0.4
0.4
0.6
0.4
0.3
0.6
0.6
0.9
0.9
0.9
0.9
0.9
0.8
0.9
0.9
0.9
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.5
0.5
0.4
0.3
0.3
0.3
0.3
0.3
43.3
42.6
43.4
41.0
40.0
41.6
45.5
45.8
46.9
42.3
48.8
54.7
56.2
57.6
57.1
51.5
50.3
50.2
49.1
46.8
49.0
48.1
44.1
43.1
42.1
43.0
41.3
38.7
38.4
39.3
38.1
36.1
37.7
37.8
36.0
0.7
0.4
0.4
0.3
0.3
0.3
0.3
0.5
0.4
0.4
0.3
0.3
0.3
0.4
0.2
0.3
0.3
0.5
0.4
0.2
0.3
0.6
0.4
0.4
0.5
0.3
0.4
0.5
0.4
0.5
0.5
0.5
0.6
0.7
0.7
21.3
20.5
20.1
20.0
20.3
21.2
22.3
23.3
24.8
26.6
28.3
30.0
31.8
33.7
35.7
37.5
39.4
41.4
42.8
44.4
45.9
47.1
48.4
49.3
49.8
49.8
49.1
48.4
47.8
47.3
46.6
46.0
45.2
44.4
44.1
D
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.3
0.4
0.4
0.4
0.5
Case
26.4
25.5
24.8
24.0
24.2
25.0
25.8
27.1
28.6
30.4
31.9
33.5
35.4
37.2
39.1
40.7
42.6
44.7
46.6
48.0
49.4
50.8
51.9
52.6
53.2
53.8
54.2
54.7
55.0
55.2
54.9
54.6
54.5
54.0
53.4
E
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
Case
26.7
25.1
25.6
24.5
23.8
24.4
25.7
25.6
28.7
29.8
32.2
35.0
36.7
38.6
37.4
41.4
44.1
45.3
44.9
46.1
50.5
49.7
49.1
51.2
51.5
50.9
54.5
54.2
55.9
51.9
56.5
55.4
55.5
54.8
53.9
F
0.6
0.5
0.7
0.7
0.7
0.9
0.7
0.6
0.5
0.6
0.4
0.8
0.5
0.6
0.6
0.4
0.4
0.5
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.6
0.3
0.6
0.8
0.7
0.5
0.7
0.6
0.4
0.2
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.5
0.5
0.5
0.5
0.6
0.7
0.6
0.6
0.7
0.7
0.6
0.5
0.6
0.7
23.6
23.0
22.5
22.0
22.3
23.0
24.1
25.6
27.3
29.4
31.5
33.6
35.5
37.5
39.6
41.3
43.0
44.6
46.1
47.6
49.1
50.4
51.4
52.0
52.6
52.8
52.9
52.3
51.9
51.7
51.4
50.8
50.2
49.6
49.2
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
24.3
22.7
23.2
22.3
21.6
22.4
23.6
23.7
26.9
27.9
30.2
32.9
35.0
36.9
36.5
40.5
42.9
44.0
44.0
45.3
49.7
48.8
48.8
50.3
50.9
50.5
54.1
53.8
55.8
52.0
56.5
55.4
55.5
54.8
54.0
0.6
0.5
0.7
0.6
0.7
0.9
0.7
0.6
0.6
0.6
0.4
0.9
0.5
0.6
0.5
0.4
0.5
0.5
0.3
0.4
0.4
0.4
0.3
0.4
0.4
0.7
0.3
0.6
0.8
0.7
0.4
0.6
0.6
0.4
0.3
Points
R1
R2
1.80 1.64
1.80 1.66
1.80 1.68
1.80 1.72
1.80 1.76
1.80 1.80
1.80 1.84
1.80 1.88
1.80 1.92
1.80 1.96
1.80 2.00
1.80 2.04
1.80 2.08
1.80 2.12
1.80 2.16
1.80 2.20
1.80 2.25
1.80 2.30
1.80 2.35
1.80 2.40
1.80 2.45
1.80 2.50
1.80 2.55
1.80 2.60
1.80 2.65
1.80 2.70
1.80 2.80
1.80 2.90
1.80 3.00
1.80 3.10
1.80 3.20
1.80 3.30
1.80 3.40
1.80 3.50
1.80 3.60
Free energy
Case A
51.6 0.2
50.0 0.2
48.7 0.2
46.4 0.2
44.8 0.2
43.8 0.2
43.1 0.2
42.6 0.2
42.3 0.2
42.3 0.2
42.2 0.2
42.2 0.2
42.2 0.2
42.1 0.2
40.8 0.2
38.1 0.2
35.6 0.1
33.3 0.2
31.1 0.2
28.5 0.2
25.6 0.2
22.9 0.2
20.6 0.2
18.5 0.2
16.4 0.3
14.6 0.3
11.7 0.2
8.8
0.3
6.9
0.4
5.6
0.4
4.0
0.4
3.2
0.4
2.2
0.4
1.8
0.5
1.7
0.5
with ave+/-std (kcal/mol)
Case B
Case C
Case
61.0 1.0 47.2 0.4 43.4
59.4 1.0 45.5 0.4 42.0
58.0 1.0 44.0 0.4 40.8
55.8 1.0 41.8 0.4 38.9
54.4 1.0 40.2 0.3 37.7
53.3 1.0 39.2 0.3 37.0
52.4 1.0 38.3 0.3 36.8
51.9 0.9 38.0 0.3 36.7
51.4 0.9 38.0 0.3 36.9
51.2 0.9 38.1 0.2 37.1
49.7 1.0 38.0 0.2 37.5
47.0 1.0 38.0 0.2 38.2
44.4 1.0 38.1 0.2 38.9
42.9 1.0 37.9 0.2 39.5
41.9 1.0 37.8 0.2 39.9
39.5 1.0 36.8 0.2 40.5
36.5 1.0 33.7 0.2 41.5
33.4 1.0 31.1 0.2 42.1
30.7 0.9 28.7 0.3 42.6
28.0 0.9 26.1 0.3 42.8
25.4 0.9 23.9 0.3 43.2
23.0 0.8 21.6 0.3 42.2
20.6 0.8 19.1 0.3 40.5
18.6 0.8 16.9 0.3 40.4
16.8 0.7 15.0 0.4 40.1
15.3 0.7 13.3 0.4 39.5
12.2 0.7 10.5 0.4 37.8
9.8
0.7 7.9
0.4 35.8
7.7
0.7 5.9
0.3 33.8
6.1
0.7 4.3
0.3 32.7
4.7
0.6 3.6
0.3 31.3
3.7
0.4 2.6
0.5 30.6
2.7
0.3 1.9
0.6 29.8
1.7
0.2 1.8
0.7 28.7
1.2
0.2 1.9
0.8 27.8
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
50.8
49.4
48.4
45.9
44.5
43.5
43.0
42.6
42.3
42.6
42.5
42.6
42.7
42.6
41.4
38.7
36.2
33.8
31.9
29.1
26.7
23.7
21.3
19.5
17.3
15.7
12.8
9.7
8.2
6.7
5.2
4.7
3.7
3.3
3.1
53.2
51.6
50.2
48.0
46.6
45.8
45.6
45.5
45.4
45.3
45.6
44.2
43.2
42.3
39.9
38.0
35.3
32.8
30.4
28.2
25.8
23.2
20.9
18.7
16.5
14.6
11.9
9.7
8.0
6.1
4.6
3.5
2.8
2.5
2.5
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.1
0.1
0.2
0.1
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.6
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.3
0.4
0.3
0.2
46.6
45.1
43.7
41.4
39.7
39.0
38.2
38.0
38.2
38.2
38.0
38.2
38.5
38.3
38.3
37.1
34.2
31.7
29.4
26.8
24.7
22.5
20.1
18.0
16.1
14.5
11.7
9.1
7.0
5.5
5.2
3.8
3.4
3.1
3.3
0.5
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.5
0.4
0.4
0.3
0.3
0.5
0.6
0.7
0.8
42.4
41.0
39.9
38.1
36.9
36.6
36.7
36.8
37.2
37.8
38.6
39.5
40.5
41.3
41.9
42.7
43.6
44.4
45.1
44.7
42.6
39.8
38.5
37.6
36.2
35.9
34.0
31.2
28.7
27.6
26.0
24.5
23.6
22.2
21.5
D
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.6
0.8
1.0
0.9
1.0
0.9
0.9
1.0
1.0
Case
60.6
59.1
57.7
55.7
54.7
53.8
53.3
53.1
53.2
53.2
53.3
53.6
53.9
54.3
54.6
54.7
54.7
54.6
54.3
54.1
54.0
53.8
53.3
52.7
52.1
51.4
49.4
47.6
45.6
43.8
42.1
40.5
39.5
38.7
37.8
E
0.7
0.7
0.7
0.8
0.8
0.8
0.8
0.9
0.9
0.9
0.9
0.9
1.0
1.0
0.9
0.9
0.9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.9
0.9
0.8
0.9
0.9
0.9
1.0
1.0
Case
54.4
50.6
50.4
68.3
56.3
62.2
50.3
58.1
64.9
64.2
67.9
71.2
72.3
67.9
63.6
70.2
72.0
72.1
70.7
66.5
70.8
71.0
68.2
69.2
67.6
65.9
67.6
64.6
62.9
57.2
64.2
59.5
55.5
55.0
54.5
F
1.0
0.8
0.6
0.7
0.8
1.3
0.7
0.6
0.8
0.6
0.6
0.9
0.8
0.8
0.6
0.4
0.5
0.6
0.4
0.3
0.6
0.5
0.5
0.4
0.5
0.6
0.4
0.5
0.8
0.7
0.4
0.8
0.8
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.5
0.5
0.7
0.9
1.0
1.1
1.2
1.2
57.8
56.5
55.3
53.3
51.9
51.5
51.3
51.3
51.7
52.0
52.6
53.0
53.5
53.9
54.2
54.8
55.0
54.7
54.9
55.0
54.4
53.9
53.0
52.3
51.7
50.8
48.4
46.3
44.0
41.8
40.1
38.1
36.1
34.7
33.7
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.9
0.9
0.9
0.9
0.9
1.0
1.0
1.0
0.9
1.0
1.0
1.1
1.2
1.1
1.1
1.3
1.3
1.3
1.5
1.7
1.7
1.7
1.6
1.6
1.6
1.5
1.4
53.1
49.2
49.1
64.5
55.4
60.1
49.8
55.9
61.5
61.0
64.5
67.9
69.1
65.1
60.7
67.2
69.1
69.4
67.7
64.0
68.2
68.5
65.9
67.1
65.6
63.8
65.2
62.5
61.2
62.7
62.3
58.2
59.0
53.9
53.0
1.0
0.8
0.6
0.7
0.8
1.3
0.7
0.6
0.8
0.6
0.6
0.9
0.7
0.8
0.6
0.4
0.5
0.6
0.4
0.3
0.6
0.5
0.5
0.4
0.5
0.7
0.4
0.5
0.8
0.5
0.4
0.7
0.6
0.4
0.5
Points
R1
R2
2.60 1.64
2.60 1.66
2.60 1.68
2.60 1.72
2.60 1.76
2.60 1.80
2.60 1.84
2.60 1.88
2.60 1.92
2.60 1.96
2.60 2.00
2.60 2.04
2.60 2.08
2.60 2.12
2.60 2.16
2.60 2.20
2.60 2.25
2.60 2.30
2.60 2.35
2.60 2.40
2.60 2.45
2.60 2.50
2.60 2.55
2.60 2.60
2.60 2.65
2.60 2.70
2.60 2.80
2.60 2.90
2.60 3.00
2.60 3.10
2.60 3.20
2.60 3.30
2.60 3.40
2.60 3.50
2.60 3.60
Free energy
Case A
45.8 0.2
48.2 0.5
46.7 0.6
43.6 0.6
45.3 0.6
44.1 0.9
47.3 0.6
52.7 0.4
51.2 0.5
55.3 0.4
57.5 0.4
55.3 0.4
60.1 0.5
61.1 0.2
59.3 0.2
53.7 0.5
52.1 0.4
51.3 0.1
51.5 0.4
51.0 0.4
49.3 0.2
46.9 0.3
46.5 0.6
43.1 0.4
45.3 0.7
44.2 0.5
42.7 0.4
37.9 0.3
37.9 0.4
36.5 0.4
36.0 0.5
37.1 0.4
36.4 0.4
34.9 0.6
34.9 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
84.0 0.5 42.9 0.6 20.0
81.5 0.4 41.6 0.4 19.3
79.2 0.4 42.3 0.4 18.8
74.6 0.4 39.1 0.3 18.4
71.2 0.4 39.9 0.4 18.5
68.2 0.4 41.4 0.3 19.2
65.6 0.5 45.3 0.3 20.4
63.2 0.5 45.4 0.5 21.7
61.0 0.5 45.7 0.4 23.3
59.3 0.5 40.7 0.4 25.0
57.8 0.5 48.7 0.3 26.9
56.5 0.5 55.2 0.3 29.0
55.5 0.5 56.7 0.3 31.0
54.3 0.5 57.8 0.5 32.9
53.4 0.5 57.4 0.2 34.8
52.5 0.5 52.0 0.3 36.5
51.5 0.5 50.6 0.3 38.5
50.8 0.6 50.6 0.5 40.4
50.0 0.6 50.2 0.4 42.2
49.4 0.6 47.4 0.2 44.0
48.8 0.5 49.6 0.3 45.6
48.2 0.5 48.8 0.5 46.7
47.6 0.5 44.6 0.4 47.6
47.1 0.5 44.2 0.4 48.6
46.5 0.6 42.9 0.5 49.2
45.8 0.6 44.5 0.4 49.5
43.6 0.5 42.5 0.4 50.3
42.3 0.4 40.1 0.5 50.4
41.4 0.4 39.7 0.4 50.1
40.3 0.4 40.4 0.5 49.8
39.5 0.3 39.3 0.5 49.7
38.9 0.3 37.5 0.5 49.6
38.6 0.3 39.1 0.6 49.4
38.0 0.2 39.4 0.7 49.4
37.5 0.2 37.1 0.7 49.5
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
44.7
46.8
44.8
41.5
43.6
43.2
46.4
50.8
49.8
55.2
56.8
55.6
60.6
61.7
59.8
53.6
52.2
51.5
52.0
51.6
49.6
47.6
47.1
43.7
46.1
44.9
43.8
38.9
38.9
37.5
37.1
38.3
37.6
35.9
36.0
85.1
82.9
81.1
76.3
72.9
69.9
67.5
65.6
63.9
62.3
60.8
59.6
58.5
57.6
56.7
55.9
54.9
54.0
53.1
52.4
51.6
50.6
49.8
48.8
47.9
47.2
45.2
43.6
42.4
41.5
40.9
40.1
39.4
39.0
38.7
S22
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.2
0.5
0.7
0.6
0.7
1.2
0.5
0.3
0.6
0.4
0.4
0.4
0.5
0.2
0.2
0.5
0.4
0.2
0.4
0.4
0.3
0.3
0.6
0.4
0.8
0.4
0.3
0.3
0.4
0.4
0.5
0.4
0.4
0.7
0.6
0.8
0.7
0.7
0.7
0.7
0.7
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.6
0.6
0.6
0.6
0.5
0.4
0.4
0.4
0.4
0.3
0.2
0.2
42.1
40.6
40.8
38.2
39.4
41.1
44.9
45.2
45.0
39.1
48.0
55.3
56.6
56.6
56.6
52.4
51.0
50.9
50.8
47.7
49.9
49.4
45.2
44.9
43.8
45.3
43.6
41.6
40.9
41.8
40.7
38.8
40.4
40.6
38.0
0.6
0.3
0.5
0.4
0.3
0.3
0.3
0.5
0.4
0.4
0.5
0.3
0.3
0.6
0.2
0.3
0.3
0.5
0.4
0.3
0.3
0.5
0.4
0.4
0.5
0.4
0.4
0.5
0.4
0.5
0.5
0.6
0.6
0.7
0.7
17.2
16.6
16.2
16.0
16.3
17.4
18.8
20.1
21.8
23.7
25.8
27.7
29.5
31.5
33.4
35.2
37.7
39.8
41.7
43.3
44.8
46.3
47.5
48.4
49.2
49.5
49.8
50.0
49.9
49.4
48.8
48.4
47.9
47.6
47.4
D
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.1
0.1
0.2
0.2
0.2
0.2
0.2
0.1
0.2
0.2
0.3
0.3
0.3
0.4
0.5
0.5
0.5
0.5
0.6
0.8
0.9
0.9
0.8
0.9
0.9
0.9
0.9
Case
22.0
21.3
20.7
20.3
20.5
21.1
22.4
23.9
25.5
27.4
29.1
31.0
33.0
34.8
36.6
38.3
40.4
42.5
44.3
45.9
47.5
48.9
49.9
50.8
51.5
52.1
52.9
53.3
53.3
52.9
52.8
52.4
51.9
52.1
51.9
E
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.3
0.4
0.5
0.5
0.5
0.5
0.5
0.5
Case
22.0
20.7
20.9
20.4
19.6
20.4
22.0
21.7
25.0
26.0
28.3
31.1
33.6
35.1
35.4
39.1
41.5
42.6
43.0
44.6
48.7
47.7
48.0
49.3
50.3
50.4
53.8
53.5
55.7
51.9
56.4
55.3
55.5
54.7
54.0
F
0.5
0.5
0.7
0.6
0.7
0.9
0.6
0.6
0.6
0.6
0.4
0.9
0.5
0.6
0.5
0.4
0.4
0.5
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.7
0.3
0.5
0.8
0.6
0.4
0.6
0.6
0.4
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.6
0.7
0.7
0.7
0.7
0.7
0.7
19.4
18.8
18.3
18.0
18.3
19.1
20.5
22.0
23.6
25.3
27.1
29.1
31.3
33.2
35.1
37.1
39.7
41.9
43.5
45.1
46.7
47.9
49.0
49.9
50.7
51.2
51.9
52.1
52.3
52.1
51.9
51.5
51.3
51.1
50.8
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.6
0.6
0.6
0.7
0.7
0.7
19.9
18.8
18.8
18.6
17.8
18.4
20.3
20.0
23.3
24.6
26.4
29.6
32.0
33.5
34.0
37.6
40.2
41.7
42.0
43.6
47.7
46.6
47.3
48.7
49.4
49.9
53.3
53.3
55.4
51.7
56.1
55.2
55.3
54.6
54.0
0.5
0.5
0.7
0.6
0.7
0.9
0.6
0.5
0.5
0.5
0.3
0.8
0.5
0.6
0.5
0.4
0.4
0.5
0.3
0.5
0.4
0.4
0.4
0.4
0.4
0.6
0.3
0.5
0.8
0.6
0.3
0.6
0.6
0.4
0.3
Points
R1
R2
1.88 1.64
1.88 1.66
1.88 1.68
1.88 1.72
1.88 1.76
1.88 1.80
1.88 1.84
1.88 1.88
1.88 1.92
1.88 1.96
1.88 2.00
1.88 2.04
1.88 2.08
1.88 2.12
1.88 2.16
1.88 2.20
1.88 2.25
1.88 2.30
1.88 2.35
1.88 2.40
1.88 2.45
1.88 2.50
1.88 2.55
1.88 2.60
1.88 2.65
1.88 2.70
1.88 2.80
1.88 2.90
1.88 3.00
1.88 3.10
1.88 3.20
1.88 3.30
1.88 3.40
1.88 3.50
1.88 3.60
Free energy
Case A
50.5 0.3
49.1 0.3
48.3 0.3
45.9 0.2
44.4 0.3
43.4 0.2
43.1 0.2
42.6 0.3
42.7 0.2
43.1 0.2
43.2 0.2
43.2 0.2
43.5 0.2
43.4 0.2
42.2 0.2
39.3 0.2
37.0 0.1
34.8 0.1
33.0 0.2
30.1 0.2
27.8 0.3
24.8 0.2
22.3 0.3
20.7 0.2
18.6 0.2
17.2 0.3
14.1 0.3
10.9 0.3
9.7
0.4
8.1
0.4
6.6
0.4
6.5
0.4
5.4
0.5
4.7
0.5
4.6
0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
66.0 1.0 46.2 0.5 41.6
64.5 1.0 44.8 0.4 40.3
63.2 1.0 43.6 0.4 39.0
59.2 1.0 41.3 0.4 37.2
55.8 1.0 39.7 0.4 36.4
55.5 0.9 39.1 0.3 35.9
55.1 0.9 38.2 0.3 35.9
55.0 0.8 38.3 0.4 36.0
55.2 0.8 38.6 0.3 36.3
54.2 0.8 38.6 0.2 37.2
51.6 0.8 38.4 0.1 38.0
49.3 0.8 38.8 0.3 38.9
47.1 0.8 39.3 0.2 40.0
44.9 0.8 39.1 0.2 40.7
42.8 0.7 39.0 0.2 41.3
40.5 0.7 37.6 0.2 42.0
37.8 0.8 35.0 0.2 42.8
35.3 0.8 32.6 0.3 43.2
32.6 0.8 30.5 0.3 43.5
30.3 0.8 27.8 0.3 44.0
28.1 0.8 26.1 0.3 43.0
25.8 0.8 23.7 0.3 40.2
23.8 0.8 21.1 0.4 39.3
21.9 0.8 19.4 0.4 38.2
20.1 0.8 17.4 0.4 36.8
18.5 0.8 16.3 0.3 36.1
15.4 0.7 13.2 0.5 32.1
12.5 0.6 10.5 0.4 29.6
10.3 0.4 8.6
0.4 27.9
8.6
0.4 7.2
0.3 26.6
7.1
0.4 6.9
0.3 25.5
5.7
0.4 5.6
0.5 24.8
4.8
0.3 5.2
0.6 24.3
4.3
0.2 5.0
0.7 23.8
4.0
0.2 5.0
0.8 23.4
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
50.5
49.0
48.3
45.9
44.4
43.8
43.6
43.0
43.4
43.8
44.1
44.0
44.7
44.3
43.2
40.4
38.1
36.2
34.1
31.2
29.1
26.2
23.6
22.1
20.4
18.7
15.7
12.1
11.4
9.6
8.1
8.3
7.3
6.6
6.4
62.3
60.9
59.6
57.4
56.1
55.4
55.3
53.6
51.2
49.4
46.4
45.5
44.7
42.3
40.3
38.3
35.8
33.3
30.7
28.5
26.6
24.7
22.8
21.2
19.9
18.6
15.8
13.3
11.2
9.9
8.8
7.5
6.8
6.2
5.8
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.3
0.3
0.2
0.2
0.3
0.2
0.3
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.7
0.9
0.8
0.9
0.9
0.9
0.9
0.9
0.8
0.8
0.9
0.8
0.8
0.8
0.8
0.7
0.8
0.8
0.7
0.7
0.7
0.6
0.5
0.3
0.3
0.2
0.3
46.0
44.8
43.6
41.4
39.9
39.4
38.7
38.8
39.1
39.3
39.2
39.7
40.1
40.3
40.1
38.4
36.0
33.6
31.7
29.0
27.7
25.0
22.4
21.0
18.9
18.2
14.8
12.1
10.3
9.1
8.8
7.7
7.3
6.9
6.8
0.5
0.4
0.4
0.4
0.4
0.3
0.2
0.4
0.3
0.2
0.1
0.3
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.5
0.6
0.7
0.8
40.3
39.0
37.9
36.5
35.7
35.5
35.7
36.3
37.0
38.0
39.0
40.0
41.2
42.3
43.2
44.0
44.9
45.7
46.6
47.4
46.4
45.2
45.3
44.9
44.4
44.3
43.2
41.4
40.2
38.6
37.8
36.9
35.1
33.8
32.9
D
0.5
0.5
0.5
0.5
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.7
Case
56.6
55.1
54.0
52.2
51.1
50.5
50.7
50.9
51.0
51.5
52.1
52.6
53.1
53.6
54.1
54.3
54.4
54.3
54.4
54.3
54.2
53.7
53.1
52.3
51.4
50.6
48.6
46.4
44.4
42.3
40.7
39.5
38.3
37.3
36.3
E
0.6
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.6
0.7
0.7
0.7
0.8
0.9
1.0
1.1
1.2
Case
51.6
48.0
48.4
61.1
54.9
58.8
49.7
55.7
58.1
58.3
61.7
64.7
66.2
62.7
58.4
64.7
66.7
66.9
65.2
61.9
66.1
66.4
63.9
65.4
63.7
62.0
63.4
61.1
59.9
54.9
54.4
57.2
57.8
53.2
52.0
F
0.9
0.8
0.6
0.6
0.8
1.1
0.7
0.6
0.8
0.6
0.6
0.9
0.7
0.8
0.7
0.3
0.5
0.6
0.4
0.3
0.6
0.5
0.5
0.4
0.5
0.7
0.4
0.5
0.8
0.7
0.7
0.7
0.6
0.4
0.5
0.4
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.8
0.9
54.1
52.7
51.6
49.9
48.8
48.3
48.2
48.3
48.7
49.0
49.5
50.2
50.8
51.5
52.2
52.7
53.2
53.9
54.3
54.2
54.0
53.9
53.4
53.0
52.4
51.3
49.7
47.5
45.1
43.0
40.7
39.0
37.6
36.2
35.7
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.7
0.8
0.8
0.9
1.0
1.0
1.2
1.2
1.2
50.3
47.2
47.9
58.0
54.7
56.2
49.4
54.0
55.1
55.8
59.1
61.9
63.5
60.5
56.4
62.4
64.3
64.7
63.1
60.1
64.1
64.5
62.1
64.0
62.4
60.5
61.9
60.0
59.1
54.3
59.5
56.8
57.0
52.8
51.4
0.7
0.8
0.6
0.6
0.8
0.9
0.7
0.7
0.8
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.6
0.4
0.3
0.6
0.5
0.5
0.4
0.5
0.7
0.4
0.5
0.8
0.6
0.4
0.7
0.6
0.4
0.4
Points
R1
R2
2.70 1.64
2.70 1.66
2.70 1.68
2.70 1.72
2.70 1.76
2.70 1.80
2.70 1.84
2.70 1.88
2.70 1.92
2.70 1.96
2.70 2.00
2.70 2.04
2.70 2.08
2.70 2.12
2.70 2.16
2.70 2.20
2.70 2.25
2.70 2.30
2.70 2.35
2.70 2.40
2.70 2.45
2.70 2.50
2.70 2.55
2.70 2.60
2.70 2.65
2.70 2.70
2.70 2.80
2.70 2.90
2.70 3.00
2.70 3.10
2.70 3.20
2.70 3.30
2.70 3.40
2.70 3.50
2.70 3.60
Free energy
Case A
43.2 0.3
45.8 0.5
42.7 0.7
39.5 0.6
42.7 0.8
41.9 1.3
45.9 0.6
48.9 0.3
48.0 0.6
55.1 0.4
55.0 0.4
55.7 0.4
59.9 0.6
62.2 0.2
60.0 0.2
53.7 0.5
52.3 0.4
51.6 0.2
52.4 0.5
52.1 0.4
49.8 0.3
47.9 0.3
47.9 0.7
44.3 0.4
47.1 0.8
45.3 0.4
44.6 0.3
39.6 0.4
39.6 0.4
38.3 0.4
38.3 0.6
39.2 0.4
38.6 0.4
36.9 0.7
36.9 0.7
with ave+/-std (kcal/mol)
Case B
Case C
Case
87.8 0.5 41.4 0.6 15.4
85.1 0.5 39.5 0.3 14.6
82.6 0.5 39.9 0.6 14.1
78.2 0.4 37.6 0.4 14.2
74.5 0.4 38.9 0.3 14.7
71.4 0.4 40.6 0.4 15.7
68.9 0.5 44.1 0.2 17.2
66.5 0.5 44.2 0.5 18.7
64.5 0.5 42.9 0.4 20.2
62.9 0.4 37.4 0.4 22.1
61.6 0.4 47.3 0.6 24.4
60.6 0.4 55.3 0.3 26.5
59.4 0.4 56.8 0.4 28.5
58.2 0.4 55.7 0.6 30.5
57.2 0.4 55.7 0.3 32.6
56.5 0.4 52.8 0.3 34.7
55.5 0.4 51.1 0.3 37.2
54.6 0.4 51.2 0.4 39.6
53.5 0.4 51.3 0.5 41.6
52.4 0.4 48.0 0.3 43.2
51.6 0.4 50.2 0.4 44.8
50.6 0.5 50.1 0.5 46.0
49.8 0.4 45.8 0.4 47.2
48.8 0.4 45.5 0.4 48.8
47.9 0.4 44.4 0.5 50.1
47.1 0.4 46.1 0.4 51.1
45.9 0.4 44.8 0.4 52.3
44.7 0.3 42.5 0.5 53.0
43.1 0.3 41.8 0.4 53.6
41.8 0.3 42.9 0.5 54.2
40.6 0.3 42.0 0.5 54.3
40.1 0.2 39.7 0.6 54.1
40.0 0.3 41.7 0.6 53.8
39.7 0.3 41.7 0.8 54.0
39.8 0.2 39.0 0.8 54.3
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
40.4
42.6
39.1
35.5
39.8
38.7
42.2
46.0
44.8
53.5
52.3
55.1
56.9
61.1
60.4
54.1
52.7
51.8
52.7
52.9
50.7
48.0
49.1
45.1
48.2
46.6
45.6
40.6
40.9
39.7
40.4
40.5
39.9
39.2
38.4
83.5
80.7
78.2
73.8
70.2
67.2
64.7
62.6
61.0
59.4
58.2
57.2
56.2
55.4
54.8
54.1
53.2
52.4
51.6
50.4
49.6
48.9
48.2
47.8
47.5
47.0
45.9
44.9
44.0
43.1
42.8
42.3
41.4
41.3
41.6
S23
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.4
0.6
0.7
0.6
1.1
1.2
0.7
0.3
0.6
0.4
0.5
0.6
0.7
0.3
0.3
0.5
0.4
0.3
0.6
0.4
0.3
0.3
0.8
0.5
0.8
0.5
0.4
0.5
0.5
0.4
0.7
0.5
0.5
0.7
0.8
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.6
0.5
0.4
0.3
0.3
0.2
0.2
0.2
39.8
35.8
38.5
34.6
38.0
39.8
41.7
40.1
39.9
34.5
46.7
54.0
56.8
56.3
55.4
53.2
50.6
51.5
51.9
48.1
50.7
51.3
46.6
46.6
45.2
47.2
46.6
43.7
43.0
44.3
44.1
41.5
43.7
43.5
40.8
0.7
0.4
0.6
0.6
0.3
0.3
0.4
0.6
0.4
0.5
0.6
0.3
0.5
0.8
0.4
0.3
0.3
0.4
0.4
0.2
0.4
0.6
0.4
0.4
0.6
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.6
0.8
0.8
12.0
11.2
10.9
11.1
11.8
12.9
14.3
16.1
17.9
19.7
21.7
23.6
25.6
27.3
29.0
30.8
33.1
35.4
37.8
39.6
41.2
42.4
43.5
44.6
45.1
45.5
46.6
48.0
48.4
48.3
47.9
47.4
46.9
46.7
46.6
D
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.4
0.4
0.5
0.5
0.6
0.6
0.6
0.6
0.6
Case
17.2
16.5
16.1
16.2
16.6
17.4
18.5
20.1
21.7
23.4
25.5
27.6
29.4
31.1
33.0
34.7
36.7
38.8
40.7
42.3
43.7
45.1
46.6
47.8
48.7
49.6
51.0
51.8
52.2
52.7
53.4
53.5
53.5
53.6
53.4
E
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.7
0.7
0.7
Case
17.9
16.9
16.9
16.8
16.0
16.7
18.6
18.7
21.8
23.0
24.8
27.8
30.7
32.0
32.7
36.2
39.0
40.6
41.3
42.8
46.5
45.7
46.6
48.0
48.3
49.4
52.8
52.7
54.9
51.8
55.8
55.0
55.1
54.7
54.0
F
0.6
0.5
0.6
0.6
0.7
0.9
0.6
0.5
0.5
0.5
0.3
0.8
0.5
0.6
0.4
0.4
0.4
0.5
0.3
0.5
0.5
0.4
0.4
0.4
0.4
0.6
0.3
0.4
0.8
0.6
0.3
0.6
0.6
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.8
0.8
0.8
0.7
0.7
0.7
0.8
0.8
0.8
0.9
0.9
0.9
14.7
14.1
13.6
13.4
13.5
14.3
15.5
17.2
19.2
21.3
23.5
25.8
28.0
30.0
32.0
34.0
36.7
39.2
41.6
43.9
46.0
47.8
49.0
50.2
51.5
52.6
54.4
55.5
55.7
55.7
55.5
55.6
55.9
56.1
55.8
0.6
0.6
0.6
0.5
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.3
0.3
0.3
0.4
0.4
0.5
0.7
0.8
0.8
0.9
0.9
0.9
0.9
0.9
14.4
13.4
13.4
13.8
13.0
13.7
15.7
15.7
19.3
19.4
22.2
24.5
28.0
29.0
30.2
33.7
36.4
38.1
39.9
41.8
44.3
44.3
45.0
46.8
46.7
49.1
51.7
51.0
54.0
51.6
55.6
54.8
54.3
54.9
54.0
0.6
0.6
0.6
0.5
0.6
0.8
0.6
0.5
0.5
0.5
0.4
0.8
0.4
0.5
0.4
0.3
0.5
0.4
0.4
0.4
0.5
0.3
0.5
0.4
0.3
0.6
0.3
0.4
0.6
0.5
0.3
0.6
0.6
0.5
0.2
Points
R1
R2
1.96 1.64
1.96 1.66
1.96 1.68
1.96 1.72
1.96 1.76
1.96 1.80
1.96 1.84
1.96 1.88
1.96 1.92
1.96 1.96
1.96 2.00
1.96 2.04
1.96 2.08
1.96 2.12
1.96 2.16
1.96 2.20
1.96 2.25
1.96 2.30
1.96 2.35
1.96 2.40
1.96 2.45
1.96 2.50
1.96 2.55
1.96 2.60
1.96 2.65
1.96 2.70
1.96 2.80
1.96 2.90
1.96 3.00
1.96 3.10
1.96 3.20
1.96 3.30
1.96 3.40
1.96 3.50
1.96 3.60
Free energy
Case A
50.6 0.3
48.8 0.3
48.6 0.2
46.2 0.2
44.7 0.2
44.3 0.3
44.3 0.2
43.8 0.3
44.2 0.2
44.5 0.3
45.2 0.2
44.9 0.2
46.1 0.2
45.2 0.2
44.5 0.2
41.8 0.2
39.2 0.2
37.5 0.1
35.4 0.2
32.7 0.2
30.8 0.2
27.9 0.2
25.1 0.2
23.7 0.2
22.0 0.2
20.4 0.4
17.6 0.4
13.7 0.2
13.2 0.4
11.3 0.4
9.6
0.5
10.3 0.4
9.2
0.5
8.5
0.5
8.4
0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
59.2 0.8 45.7 0.4 40.0
57.8 0.8 44.9 0.4 38.7
56.6 0.8 43.9 0.4 37.7
54.1 0.7 41.6 0.3 36.5
52.1 0.7 40.1 0.4 35.6
51.5 0.7 39.8 0.3 35.5
51.8 0.6 39.4 0.2 35.5
50.0 0.7 39.3 0.3 35.8
48.7 0.7 39.9 0.3 36.6
47.7 0.6 40.2 0.3 37.6
46.3 0.6 40.0 0.1 38.4
47.2 0.6 40.8 0.3 39.4
46.2 0.6 41.3 0.2 40.7
43.9 0.6 41.5 0.3 41.9
41.9 0.5 41.3 0.2 43.3
40.0 0.5 39.6 0.2 44.6
38.0 0.5 37.2 0.2 45.5
35.7 0.5 34.8 0.3 46.7
33.5 0.5 32.8 0.2 48.1
31.5 0.5 30.5 0.3 49.1
29.4 0.5 29.2 0.3 49.5
27.3 0.5 26.5 0.3 49.8
25.4 0.5 24.0 0.4 50.3
23.6 0.5 22.6 0.4 50.3
21.9 0.5 20.7 0.3 50.4
20.5 0.6 20.2 0.4 50.3
17.5 0.5 16.7 0.4 49.0
14.9 0.4 13.7 0.4 47.6
13.5 0.4 12.2 0.4 46.2
11.8 0.3 11.3 0.3 44.4
10.3 0.4 10.8 0.4 42.9
8.9
0.3 10.0 0.5 41.7
8.1
0.3 9.4
0.6 40.6
8.0
0.3 8.8
0.7 39.9
7.9
0.3 8.7
0.8 39.2
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
50.9
48.7
49.0
46.6
45.2
44.8
44.8
44.7
45.1
45.3
46.5
45.9
47.5
46.4
45.8
43.1
40.1
38.8
36.9
34.2
32.5
29.7
26.9
25.3
23.9
22.1
19.3
15.5
15.1
13.1
11.3
12.2
11.0
10.3
10.4
83.0
79.8
76.8
73.5
71.2
67.0
63.8
60.6
57.9
55.4
53.0
50.6
48.4
46.3
44.1
42.0
39.8
37.9
35.7
33.4
31.5
29.7
27.7
25.8
24.0
22.4
20.0
17.3
15.1
13.8
13.0
12.3
11.4
10.4
9.9
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.3
0.2
0.2
0.2
0.3
0.2
0.3
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.4
0.4
0.2
0.4
0.4
0.5
0.4
0.5
0.4
0.6
0.7
0.6
0.6
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.5
0.6
0.5
0.5
0.5
0.4
0.4
0.3
0.3
45.9
45.0
44.2
42.0
40.4
40.4
40.1
39.9
40.7
41.1
41.0
42.0
42.5
43.0
42.8
40.6
38.4
36.0
34.0
32.1
30.6
28.2
25.8
24.2
22.5
22.0
18.7
15.5
14.5
13.6
12.9
12.2
11.5
11.0
10.7
0.4
0.4
0.5
0.3
0.4
0.3
0.2
0.3
0.4
0.3
0.1
0.3
0.2
0.3
0.2
0.2
0.2
0.3
0.2
0.3
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.3
0.4
0.5
0.6
0.8
0.8
39.9
38.7
37.8
36.4
35.6
35.6
35.7
36.1
37.1
38.3
39.5
40.9
42.1
43.3
44.6
45.9
46.2
46.4
47.6
48.4
49.2
49.6
50.0
48.9
48.1
48.4
47.1
45.7
43.7
42.6
41.8
41.1
40.9
41.0
41.3
D
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.5
0.4
0.5
0.4
0.5
0.5
0.6
0.6
Case
52.3
51.0
49.9
48.3
47.5
47.1
47.0
47.3
47.6
48.3
49.0
49.6
50.2
50.7
51.3
51.9
52.5
52.9
53.3
53.7
53.6
53.1
52.8
52.4
51.7
51.2
49.7
47.7
45.6
44.0
42.6
41.2
39.8
38.6
37.4
E
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.3
0.4
0.4
0.3
0.3
0.4
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.5
0.5
0.5
0.6
Case
49.5
46.6
47.5
55.2
53.3
53.7
49.2
51.1
52.9
53.4
56.7
59.4
61.2
58.4
54.4
60.3
62.1
62.7
61.1
58.6
62.5
62.6
60.5
62.5
61.3
59.2
60.8
59.2
58.4
53.6
58.4
56.6
56.3
52.3
51.3
F
0.7
0.8
0.6
0.6
0.8
0.9
0.7
0.7
0.7
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.6
0.4
0.3
0.6
0.5
0.5
0.4
0.5
0.7
0.3
0.6
0.8
0.6
0.4
0.7
0.6
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.3
0.3
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.5
0.5
0.6
0.7
0.6
0.6
0.6
52.3
51.0
50.0
48.6
47.6
47.1
47.2
47.5
47.9
48.6
49.4
49.9
50.7
51.5
52.0
52.4
53.1
53.7
54.1
54.6
54.9
54.7
54.3
53.9
53.7
53.2
51.2
49.7
47.8
46.4
45.1
44.1
43.0
42.3
42.0
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.5
0.6
0.7
0.7
0.7
0.7
0.7
0.8
0.9
48.8
46.2
47.5
52.5
50.6
51.0
49.7
48.6
51.0
51.3
54.4
57.0
58.8
56.4
52.5
58.4
60.3
60.7
59.2
57.3
61.2
60.9
59.2
61.4
60.2
58.1
59.8
58.4
57.8
53.1
57.7
56.5
56.0
52.1
51.5
0.8
0.8
0.6
0.6
0.8
0.9
0.7
0.7
0.5
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.6
0.4
0.4
0.6
0.5
0.5
0.4
0.5
0.7
0.3
0.6
0.8
0.7
0.5
0.7
0.6
0.4
0.4
Points
R1
R2
2.90 1.64
2.90 1.66
2.90 1.68
2.90 1.72
2.90 1.76
2.90 1.80
2.90 1.84
2.90 1.88
2.90 1.92
2.90 1.96
2.90 2.00
2.90 2.04
2.90 2.08
2.90 2.12
2.90 2.16
2.90 2.20
2.90 2.25
2.90 2.30
2.90 2.35
2.90 2.40
2.90 2.45
2.90 2.50
2.90 2.55
2.90 2.60
2.90 2.65
2.90 2.70
2.90 2.80
2.90 2.90
2.90 3.00
2.90 3.10
2.90 3.20
2.90 3.30
2.90 3.40
2.90 3.50
2.90 3.60
Free energy
Case A
38.4 0.6
41.0 0.7
36.2 0.6
32.6 0.6
36.9 1.1
36.9 1.2
39.8 0.8
43.5 0.5
41.8 0.6
51.2 0.5
49.8 0.6
54.2 0.6
56.1 0.9
60.2 0.5
60.8 0.3
53.7 0.6
52.9 0.4
51.3 0.3
52.8 0.5
52.9 0.4
50.7 0.3
48.2 0.4
49.8 0.7
45.4 0.5
48.7 0.8
47.7 0.6
46.1 0.4
41.1 0.5
41.8 0.5
40.8 0.3
41.6 0.7
41.6 0.5
41.3 0.5
40.8 0.7
39.6 0.8
with ave+/-std (kcal/mol)
Case B
Case C
Case
78.4 0.8 37.1 0.8 10.1
75.9 0.8 33.3 0.5 9.6
73.6 0.8 36.2 0.7 9.2
69.6 0.8 31.8 0.8 8.9
66.3 0.8 36.1 0.3 9.4
63.6 0.8 37.7 0.4 10.3
61.4 0.8 39.7 0.6 11.7
59.7 0.7 38.1 0.7 13.3
58.2 0.8 37.6 0.5 15.2
57.0 0.7 31.8 0.6 17.4
56.0 0.7 44.7 0.8 19.6
55.0 0.7 51.5 0.4 21.5
54.0 0.7 55.4 0.5 23.6
53.1 0.7 54.0 1.0 25.8
52.2 0.7 53.3 0.3 27.9
51.4 0.7 52.6 0.4 29.8
51.0 0.7 50.1 0.3 31.9
50.2 0.7 51.2 0.4 33.9
49.8 0.7 52.0 0.5 35.9
49.5 0.7 48.0 0.2 38.0
49.1 0.7 51.2 0.4 40.0
48.8 0.7 52.1 0.6 41.7
48.4 0.7 46.9 0.4 43.1
48.2 0.7 47.2 0.3 44.5
47.9 0.7 45.5 0.7 45.5
47.6 0.7 47.9 0.4 46.6
47.3 0.8 47.7 0.5 48.7
46.8 0.7 45.2 0.4 50.0
45.9 0.6 44.1 0.5 51.1
45.4 0.5 45.7 0.6 51.7
44.8 0.5 46.0 0.5 52.0
44.3 0.5 43.3 0.5 52.1
43.8 0.4 45.6 0.7 52.4
43.2 0.2 45.0 0.8 52.5
43.3 0.2 41.8 0.8 52.7
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
36.5
38.3
33.5
30.8
34.3
34.6
37.3
41.3
39.6
50.2
47.4
53.7
55.5
59.8
61.0
52.8
52.6
50.5
52.6
53.1
50.5
48.0
50.1
45.8
48.7
48.4
46.9
42.0
42.3
41.1
42.8
42.3
42.8
41.7
40.5
76.6
74.1
71.8
67.9
64.6
61.9
60.0
58.5
57.2
56.1
55.3
54.4
53.7
53.0
52.4
52.1
51.8
51.5
51.2
50.9
50.5
50.1
50.0
49.8
49.6
49.4
49.3
48.7
47.8
47.4
46.8
45.9
45.4
45.1
44.7
S24
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.6
0.7
0.5
0.6
1.3
1.3
0.8
0.5
0.6
0.5
0.6
0.6
1.0
0.5
0.4
0.5
0.4
0.4
0.5
0.4
0.3
0.5
0.7
0.6
0.8
0.6
0.5
0.5
0.5
0.4
0.7
0.5
0.5
0.7
0.8
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.5
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.5
0.5
0.5
0.5
0.4
0.3
0.3
0.2
0.2
0.2
34.2
31.2
33.9
29.8
33.7
35.0
38.2
36.0
35.6
29.4
42.7
50.4
54.0
52.7
52.5
52.2
49.6
51.1
52.0
47.7
51.4
52.8
47.0
47.8
45.8
47.9
48.5
46.6
44.8
46.6
47.5
44.4
47.0
46.4
42.7
0.8
0.5
0.7
0.9
0.3
0.4
0.7
0.7
0.5
0.6
0.8
0.4
0.7
1.1
0.3
0.4
0.3
0.4
0.5
0.3
0.5
0.7
0.4
0.4
0.7
0.5
0.5
0.4
0.5
0.6
0.5
0.5
0.7
0.9
0.9
7.4
6.9
6.7
6.6
7.1
8.0
9.4
11.0
12.7
14.7
16.7
19.0
21.1
23.3
25.5
27.5
30.3
32.6
34.8
37.1
38.8
40.6
42.4
43.8
44.7
45.4
47.0
47.3
47.4
47.6
47.8
47.3
46.7
46.7
46.5
D
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.5
0.6
0.6
Case
11.5
10.8
10.5
10.4
10.7
11.5
12.6
14.4
16.5
18.5
20.7
22.9
25.1
27.3
29.7
31.9
34.2
36.9
39.3
41.3
43.4
45.4
47.4
49.3
51.0
52.5
54.1
55.0
55.6
56.2
57.1
57.4
57.2
57.0
57.0
E
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.6
Case
11.5
10.4
10.1
11.1
10.3
11.1
13.0
15.2
16.6
17.3
20.2
22.0
25.4
26.4
28.2
31.8
34.3
36.4
38.5
40.5
42.2
43.0
44.0
45.6
45.4
48.2
49.6
50.2
52.5
51.6
54.8
54.0
53.8
54.7
54.1
F
0.7
0.5
0.6
0.4
0.6
0.8
0.5
0.4
0.4
0.5
0.4
0.7
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.5
0.3
0.5
0.5
0.3
0.6
0.3
0.5
0.6
0.4
0.3
0.6
0.6
0.4
0.3
0.4
0.4
0.4
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.7
0.6
0.7
0.8
0.8
0.9
1.0
8.7
8.1
7.7
7.6
8.2
9.1
10.3
12.1
14.0
16.0
18.2
20.5
22.7
25.0
27.2
29.5
32.3
34.7
36.9
39.2
41.2
43.1
44.7
46.0
47.1
48.1
50.3
51.6
52.7
53.6
54.2
54.5
54.7
55.2
55.6
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.7
0.8
0.8
0.9
1.0
0.9
0.9
8.9
7.9
7.7
8.3
7.9
8.8
10.8
11.0
14.3
15.4
17.6
20.1
23.1
24.7
26.7
29.9
32.5
34.6
36.8
39.0
40.3
41.8
43.2
44.4
44.8
46.9
48.3
49.2
51.2
51.6
53.8
53.5
53.7
54.5
54.1
0.6
0.5
0.6
0.3
0.7
0.8
0.4
0.4
0.5
0.4
0.3
0.6
0.5
0.4
0.4
0.3
0.4
0.2
0.3
0.4
0.4
0.4
0.4
0.4
0.2
0.4
0.2
0.5
0.6
0.5
0.3
0.6
0.5
0.4
0.4
Points
R1
R2
2.04 1.64
2.04 1.66
2.04 1.68
2.04 1.72
2.04 1.76
2.04 1.80
2.04 1.84
2.04 1.88
2.04 1.92
2.04 1.96
2.04 2.00
2.04 2.04
2.04 2.08
2.04 2.12
2.04 2.16
2.04 2.20
2.04 2.25
2.04 2.30
2.04 2.35
2.04 2.40
2.04 2.45
2.04 2.50
2.04 2.55
2.04 2.60
2.04 2.65
2.04 2.70
2.04 2.80
2.04 2.90
2.04 3.00
2.04 3.10
2.04 3.20
2.04 3.30
2.04 3.40
2.04 3.50
2.04 3.60
Free energy
Case A
51.3 0.3
48.9 0.3
49.2 0.2
47.0 0.2
45.7 0.2
45.6 0.3
45.5 0.2
45.6 0.3
45.9 0.3
46.3 0.3
47.8 0.2
47.0 0.2
48.9 0.2
47.8 0.2
47.0 0.2
44.3 0.3
41.4 0.2
40.2 0.1
38.3 0.2
35.8 0.2
34.2 0.2
31.3 0.2
28.6 0.2
26.9 0.2
25.9 0.3
23.8 0.4
21.4 0.4
17.3 0.2
17.0 0.4
15.0 0.4
13.3 0.5
14.5 0.4
13.0 0.5
12.2 0.4
12.5 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
75.9 1.0 46.3 0.4 39.2
74.4 0.8 45.4 0.4 38.2
72.5 0.7 44.3 0.4 37.4
67.3 0.8 42.5 0.3 36.1
62.8 0.8 40.8 0.4 35.5
60.7 0.7 40.9 0.3 35.6
59.1 0.7 41.0 0.2 36.2
56.0 0.7 40.6 0.4 37.1
53.6 0.7 41.4 0.4 38.1
51.3 0.7 42.1 0.3 39.2
49.1 0.7 42.2 0.1 40.3
47.2 0.7 43.3 0.3 41.6
45.4 0.7 43.6 0.3 42.6
43.8 0.7 44.5 0.3 43.8
42.2 0.7 44.4 0.2 45.3
40.5 0.7 41.5 0.2 46.5
38.6 0.7 39.7 0.2 47.8
37.1 0.7 37.3 0.3 49.1
35.3 0.7 35.4 0.2 50.3
33.3 0.7 33.7 0.3 51.4
31.8 0.6 32.2 0.4 52.2
30.3 0.6 29.7 0.4 52.6
28.3 0.6 27.7 0.4 53.0
26.7 0.6 25.9 0.4 53.3
25.3 0.6 24.4 0.3 53.5
23.8 0.6 23.7 0.4 53.5
21.3 0.5 20.4 0.4 51.9
19.0 0.4 17.5 0.4 50.3
17.2 0.4 16.8 0.4 48.8
15.7 0.4 15.9 0.3 47.6
14.2 0.5 15.3 0.4 46.9
12.9 0.5 14.4 0.6 46.4
12.2 0.4 13.7 0.6 46.4
11.8 0.4 13.4 0.8 46.5
11.9 0.3 13.0 0.8 46.4
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
51.6
49.4
49.4
47.4
46.2
46.4
46.2
46.5
46.5
47.2
49.0
48.2
50.2
49.2
48.3
45.5
42.7
41.4
39.7
37.4
35.7
33.1
30.2
28.4
27.8
25.7
23.6
19.0
19.1
16.9
15.3
16.8
15.4
14.1
14.4
74.3
72.9
71.4
69.3
66.4
63.8
64.3
62.8
59.7
57.3
55.1
53.0
51.0
48.9
46.8
44.8
42.6
40.5
38.4
36.3
34.5
32.5
30.7
29.1
27.6
26.2
24.3
22.0
19.8
18.0
16.2
15.1
14.4
14.1
13.9
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.3
0.2
0.2
0.3
0.3
0.2
0.3
0.3
0.3
0.2
0.2
0.2
0.3
0.2
0.3
0.2
0.2
0.3
0.2
0.2
0.2
0.2
0.3
0.3
0.4
0.4
0.2
0.4
0.5
0.5
0.4
0.5
0.4
0.5
1.2
1.1
1.0
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.3
0.3
0.2
46.7
45.7
44.6
42.8
41.2
41.6
41.7
41.3
42.4
43.0
43.2
44.7
44.9
45.9
45.8
42.6
40.7
38.6
36.9
35.1
33.9
31.5
29.4
27.5
26.4
25.5
22.3
19.4
18.9
18.0
17.6
16.7
16.1
15.6
15.4
0.5
0.5
0.4
0.3
0.3
0.3
0.2
0.4
0.4
0.3
0.1
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.3
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.3
0.4
0.5
0.6
0.8
0.8
38.4
37.4
36.7
35.8
35.3
35.5
36.2
37.0
38.2
39.6
40.7
41.9
43.3
44.9
46.4
47.8
49.4
50.8
51.7
52.7
53.8
54.5
54.7
55.2
55.3
55.5
56.2
55.5
54.3
52.7
51.0
49.6
48.3
46.8
45.8
D
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.7
0.8
0.9
0.9
Case
49.6
48.3
47.4
46.3
45.9
45.7
45.6
46.1
46.9
47.7
48.3
49.1
50.1
50.9
51.8
52.6
53.5
54.0
54.5
55.1
55.5
55.5
55.2
55.1
54.7
54.0
52.6
51.3
50.1
49.0
47.5
46.1
45.1
44.4
43.9
E
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.6
0.7
0.6
0.7
0.7
0.6
0.6
0.6
0.6
0.8
1.0
1.1
Case
48.2
45.6
45.9
50.0
48.4
48.3
48.5
46.4
48.8
49.2
52.5
54.6
56.6
54.5
50.5
56.7
58.7
58.8
57.5
56.2
60.1
59.7
58.0
60.2
59.3
57.2
59.0
57.7
57.6
52.9
57.3
56.4
55.9
52.1
51.7
F
0.8
0.8
0.6
0.6
0.8
0.9
0.7
0.7
0.5
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.6
0.4
0.4
0.6
0.5
0.5
0.4
0.5
0.7
0.3
0.6
0.8
0.7
0.5
0.7
0.6
0.4
0.4
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.4
0.4
0.3
0.3
0.4
0.5
0.5
0.7
0.8
48.2
47.1
46.1
44.9
44.4
44.4
44.8
45.4
46.1
47.3
48.4
49.3
50.2
51.1
51.9
52.6
53.3
53.9
54.4
54.7
54.5
54.4
54.3
54.0
53.5
53.0
51.6
50.1
48.9
47.4
45.9
44.6
43.7
43.1
42.1
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.7
0.8
0.8
0.8
0.7
0.8
0.8
46.4
44.9
44.3
47.8
45.9
46.1
46.0
44.4
46.6
47.5
50.6
52.3
54.6
52.8
48.5
55.1
57.1
57.1
56.0
55.2
59.0
58.4
57.0
59.2
58.3
56.5
58.5
57.2
57.4
52.9
56.9
56.2
55.7
52.2
52.1
0.8
0.8
0.6
0.6
0.8
0.9
0.7
0.6
0.6
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.5
0.4
0.3
0.5
0.5
0.5
0.4
0.5
0.7
0.3
0.6
0.8
0.7
0.5
0.8
0.6
0.4
0.3
Points
R1
R2
3.10 1.64
3.10 1.66
3.10 1.68
3.10 1.72
3.10 1.76
3.10 1.80
3.10 1.84
3.10 1.88
3.10 1.92
3.10 1.96
3.10 2.00
3.10 2.04
3.10 2.08
3.10 2.12
3.10 2.16
3.10 2.20
3.10 2.25
3.10 2.30
3.10 2.35
3.10 2.40
3.10 2.45
3.10 2.50
3.10 2.55
3.10 2.60
3.10 2.65
3.10 2.70
3.10 2.80
3.10 2.90
3.10 3.00
3.10 3.10
3.10 3.20
3.10 3.30
3.10 3.40
3.10 3.50
3.10 3.60
Free energy
Case A
34.9 0.6
36.2 0.8
31.4 0.6
29.0 0.7
32.6 1.4
32.7 1.3
35.4 0.8
39.1 0.4
38.3 0.6
48.8 0.6
45.6 0.7
53.0 0.6
54.3 1.2
58.1 0.5
60.0 0.4
51.5 0.6
51.9 0.5
50.1 0.5
52.0 0.5
53.0 0.5
50.1 0.4
47.7 0.5
50.6 0.7
46.2 0.5
48.5 0.8
48.8 0.6
47.1 0.5
42.2 0.5
42.8 0.5
41.4 0.4
43.6 0.7
42.0 0.6
44.0 0.5
42.4 0.7
41.1 0.9
with ave+/-std (kcal/mol)
Case B
Case C
Case
78.7 0.8 31.9 0.8 5.6
76.2 0.8 29.7 0.8 5.2
73.9 0.8 31.9 0.8 4.9
69.9 0.7 27.9 0.9 4.6
66.8 0.7 32.0 0.3 5.2
64.1 0.7 33.1 0.4 6.3
62.1 0.7 36.7 0.9 7.7
60.5 0.8 34.3 0.8 9.4
59.2 0.8 34.4 0.4 11.1
58.0 0.7 27.2 0.6 12.8
57.1 0.7 41.3 0.9 15.0
56.3 0.7 49.1 0.4 17.4
55.5 0.7 53.0 0.7 19.7
54.9 0.7 52.3 1.1 21.8
54.3 0.7 51.5 0.3 24.0
53.9 0.7 51.7 0.5 26.2
53.6 0.7 49.0 0.4 28.9
53.1 0.7 50.7 0.4 31.5
52.8 0.7 52.0 0.5 33.8
52.3 0.6 47.1 0.4 36.0
51.7 0.7 51.6 0.5 37.5
51.3 0.7 52.7 0.7 39.2
51.2 0.6 46.7 0.5 41.1
51.1 0.6 47.9 0.4 42.5
51.1 0.6 45.9 0.7 43.9
50.9 0.6 47.8 0.6 45.1
49.9 0.5 48.8 0.5 46.4
48.2 0.5 47.6 0.5 47.6
47.4 0.5 45.0 0.6 48.0
47.2 0.4 47.1 0.6 48.2
46.6 0.4 48.5 0.5 48.2
46.0 0.2 44.8 0.5 48.1
45.8 0.2 47.8 0.7 48.4
45.6 0.2 46.8 0.9 48.7
45.6 0.2 43.3 1.0 48.5
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
33.2
34.7
30.0
27.2
31.1
30.8
33.9
37.7
37.0
47.6
45.0
51.7
52.9
57.3
58.9
50.9
51.3
49.3
51.3
52.3
49.5
47.2
50.5
45.8
48.3
48.5
47.4
42.1
43.0
41.8
43.7
41.8
44.5
42.7
41.7
80.6
78.0
75.7
72.0
69.0
66.7
64.7
63.3
62.1
61.1
60.3
59.6
59.1
58.8
58.3
57.8
57.3
56.5
56.0
55.6
55.2
54.7
54.2
53.7
53.5
53.2
52.1
51.2
50.2
49.1
48.0
47.9
47.5
46.8
46.5
S25
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.6
0.8
0.6
0.6
1.4
1.4
0.8
0.4
0.6
0.6
0.9
0.7
1.1
0.5
0.5
0.6
0.5
0.5
0.6
0.5
0.4
0.5
0.8
0.5
0.8
0.6
0.5
0.6
0.5
0.4
0.9
0.7
0.4
0.7
0.9
0.6
0.6
0.6
0.6
0.6
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.6
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.5
0.5
0.4
0.3
0.2
0.3
0.3
0.2
30.3
27.6
30.3
26.2
30.4
31.0
35.3
32.5
32.9
25.7
39.9
47.9
51.6
51.4
51.0
50.5
48.5
50.2
51.8
46.7
51.3
52.5
46.5
47.7
45.4
47.7
48.7
48.2
44.9
47.1
49.2
45.1
48.2
46.8
43.8
0.9
0.9
0.8
0.9
0.4
0.4
1.0
0.9
0.5
0.7
0.9
0.5
0.6
1.1
0.4
0.5
0.4
0.5
0.5
0.4
0.5
0.7
0.6
0.4
0.8
0.5
0.5
0.5
0.6
0.7
0.6
0.5
0.7
0.9
1.0
4.1
3.7
3.5
3.1
3.7
4.9
6.5
8.2
10.2
12.3
14.4
16.7
18.8
20.9
23.0
25.1
27.8
30.3
32.6
34.8
36.7
38.5
40.0
41.1
42.6
43.8
45.2
47.3
48.7
49.7
50.0
50.4
51.1
51.7
52.0
D
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.7
0.8
0.8
0.8
0.8
0.9
0.9
Case
6.6
5.9
5.6
5.8
6.3
7.3
8.8
10.5
12.4
14.3
16.4
18.4
20.3
22.5
24.7
26.8
29.6
32.0
34.1
35.8
37.8
39.8
41.4
42.9
44.2
45.6
48.0
48.7
49.4
49.8
50.0
50.3
50.5
50.4
50.3
E
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.5
0.5
0.5
0.5
0.5
0.6
0.7
0.7
0.8
Case
6.6
6.0
5.9
5.9
6.1
6.9
8.5
9.6
12.0
13.5
15.7
18.4
21.3
23.3
25.3
28.2
31.2
33.1
34.9
37.3
39.0
40.7
42.2
43.4
44.0
45.8
47.5
48.0
50.3
51.3
52.9
53.4
53.6
54.0
54.1
F
0.5
0.4
0.6
0.2
0.6
0.6
0.4
0.4
0.4
0.3
0.3
0.5
0.4
0.3
0.4
0.3
0.3
0.3
0.2
0.4
0.3
0.3
0.3
0.3
0.2
0.4
0.2
0.5
0.5
0.5
0.2
0.5
0.6
0.5
0.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.6
0.6
0.7
0.7
0.6
0.6
0.6
4.9
4.4
4.0
3.8
4.6
5.7
7.3
9.6
11.8
14.1
16.5
19.0
21.5
23.6
25.7
27.9
30.5
33.0
35.6
37.9
40.1
42.2
43.9
45.9
47.7
49.2
51.9
54.1
55.0
56.0
56.3
56.7
57.3
57.1
57.2
0.5
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.7
5.0
4.5
4.3
4.1
4.4
5.4
6.9
8.4
10.4
12.3
14.4
16.8
19.8
22.4
24.1
26.6
29.4
32.0
33.7
35.8
37.8
39.5
41.1
42.4
43.5
45.0
46.6
47.9
49.9
50.9
52.0
53.0
53.4
53.3
53.7
0.4
0.4
0.4
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.2
0.3
0.2
0.2
0.2
0.2
0.2
0.3
0.2
0.1
0.2
0.2
0.2
0.3
0.2
0.3
0.4
0.4
0.2
0.4
0.5
0.4
0.3
Points
R1
R2
2.12 1.64
2.12 1.66
2.12 1.68
2.12 1.72
2.12 1.76
2.12 1.80
2.12 1.84
2.12 1.88
2.12 1.92
2.12 1.96
2.12 2.00
2.12 2.04
2.12 2.08
2.12 2.12
2.12 2.16
2.12 2.20
2.12 2.25
2.12 2.30
2.12 2.35
2.12 2.40
2.12 2.45
2.12 2.50
2.12 2.55
2.12 2.60
2.12 2.65
2.12 2.70
2.12 2.80
2.12 2.90
2.12 3.00
2.12 3.10
2.12 3.20
2.12 3.30
2.12 3.40
2.12 3.50
2.12 3.60
Free energy
Case A
51.9 0.3
49.5 0.4
49.7 0.2
47.9 0.2
46.6 0.2
46.6 0.3
46.8 0.3
47.3 0.3
47.4 0.2
48.2 0.3
50.2 0.2
49.4 0.2
51.5 0.3
50.7 0.3
49.8 0.2
46.6 0.3
43.8 0.2
42.6 0.1
40.7 0.3
38.9 0.2
37.1 0.2
34.7 0.2
31.9 0.3
29.9 0.3
29.7 0.4
27.6 0.4
25.7 0.4
20.8 0.2
21.2 0.4
18.9 0.5
17.2 0.5
19.0 0.4
17.5 0.4
16.2 0.5
16.3 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
69.8 1.0 47.1 0.5 37.9
68.5 1.0 45.8 0.5 36.9
67.6 1.0 44.9 0.4 36.2
65.1 0.8 42.8 0.3 35.3
62.8 0.7 41.5 0.3 35.0
61.8 0.7 42.1 0.3 35.3
60.6 0.9 42.4 0.2 35.9
61.3 0.9 42.0 0.4 36.7
60.2 0.9 43.5 0.4 37.8
57.6 0.9 44.0 0.4 38.7
55.5 0.9 44.4 0.1 39.9
53.3 0.9 46.0 0.3 41.6
51.4 0.9 46.2 0.3 43.3
49.4 0.9 47.3 0.3 44.8
47.5 0.9 47.2 0.3 45.9
45.8 0.9 43.8 0.3 47.1
43.5 0.9 41.9 0.2 49.0
41.4 0.8 39.8 0.2 50.6
39.5 0.8 38.6 0.2 51.5
37.7 0.8 36.5 0.3 52.9
35.8 0.8 35.7 0.3 53.9
34.0 0.7 33.3 0.4 54.6
32.3 0.7 31.1 0.4 55.2
30.4 0.7 29.2 0.3 55.6
28.7 0.6 28.1 0.3 56.2
27.3 0.6 27.3 0.4 56.4
25.0 0.5 24.4 0.4 55.6
22.8 0.5 21.4 0.4 53.9
21.2 0.4 21.0 0.4 52.3
19.7 0.4 19.9 0.3 51.0
18.5 0.4 19.9 0.4 49.4
17.6 0.4 18.7 0.5 49.0
16.9 0.3 18.5 0.6 48.5
16.6 0.2 17.7 0.8 47.6
16.2 0.2 17.6 0.8 46.8
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
52.0
49.6
50.1
48.5
46.8
46.7
47.4
48.2
48.3
49.0
51.4
50.4
52.9
52.2
50.9
47.8
45.0
43.7
42.0
40.4
38.8
36.1
33.8
31.6
31.6
29.5
27.8
22.7
23.2
21.0
18.9
21.1
19.3
18.4
18.4
73.9
71.9
71.1
67.5
64.2
63.9
62.9
60.2
57.4
56.3
55.4
53.3
51.5
49.8
48.2
46.5
44.5
42.5
40.5
38.7
37.1
35.4
33.7
32.2
31.0
29.6
27.0
25.1
23.4
22.1
21.1
20.0
19.2
18.7
18.5
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.4
0.2
0.2
0.3
0.2
0.3
0.3
0.3
0.3
0.2
0.2
0.3
0.3
0.2
0.3
0.2
0.1
0.3
0.2
0.2
0.2
0.3
0.3
0.4
0.5
0.4
0.2
0.4
0.5
0.5
0.4
0.4
0.5
0.6
1.3
1.3
1.2
1.1
0.9
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.6
0.5
0.5
0.4
0.4
0.3
0.3
0.2
47.4
45.9
45.2
43.3
41.8
42.7
42.9
42.7
44.4
45.2
45.6
47.2
47.4
48.6
48.5
44.6
43.1
41.0
40.0
38.0
37.7
35.0
32.8
31.0
30.0
29.2
26.3
23.3
23.2
22.0
22.2
20.8
20.8
19.8
19.9
0.5
0.5
0.4
0.3
0.3
0.3
0.2
0.4
0.4
0.3
0.1
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.3
0.3
0.4
0.4
0.3
0.3
0.4
0.3
0.4
0.4
0.3
0.4
0.5
0.6
0.8
0.8
37.5
36.6
35.8
34.8
34.7
35.1
35.8
36.9
38.2
39.8
41.6
43.4
45.1
46.6
48.0
49.8
51.7
53.6
55.3
56.6
57.9
59.0
59.7
60.6
61.0
61.1
61.0
60.0
59.1
57.9
56.8
55.5
54.1
53.1
52.0
D
0.2
0.2
0.3
0.2
0.3
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.5
0.5
0.4
Case
47.0
45.7
44.9
44.0
43.6
43.4
43.7
44.3
45.2
46.0
47.0
48.0
49.1
50.3
51.4
52.5
53.7
54.6
55.4
56.0
56.4
56.5
56.5
56.6
56.4
56.2
55.4
54.9
53.7
52.1
50.5
48.9
47.8
46.9
46.0
E
0.4
0.5
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.4
0.4
0.5
0.4
0.4
0.4
0.5
Case
44.4
44.3
43.1
45.4
43.5
44.1
43.9
42.4
44.5
45.8
48.8
50.3
52.6
51.3
47.0
53.9
55.6
55.6
54.6
54.2
58.2
57.2
56.0
58.3
57.3
55.8
57.9
56.5
57.1
52.8
56.9
55.9
55.5
52.3
52.2
F
0.8
0.8
0.7
0.6
0.8
0.9
0.7
0.6
0.6
0.6
0.6
0.9
0.7
0.7
0.6
0.3
0.5
0.5
0.4
0.3
0.5
0.5
0.4
0.4
0.5
0.7
0.3
0.6
0.8
0.7
0.5
0.8
0.6
0.4
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.2
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.3
0.3
0.3
0.3
0.4
0.5
0.7
0.7
0.7
0.8
0.8
0.8
44.6
43.4
42.6
41.8
41.5
41.4
41.8
42.8
43.9
45.1
46.1
47.2
48.4
49.6
50.9
52.0
53.4
54.7
55.4
56.3
57.0
57.4
57.5
57.9
57.9
57.5
56.9
55.7
54.8
53.8
52.7
52.0
51.4
50.9
50.8
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.5
0.7
0.8
0.7
0.7
0.7
0.7
0.9
1.0
1.0
43.6
42.7
41.6
42.9
41.2
41.8
41.7
40.6
42.7
44.0
46.8
48.6
50.7
49.9
45.8
52.5
54.2
54.4
53.2
53.2
57.4
56.4
55.0
57.4
56.4
55.2
57.5
56.1
56.8
52.5
56.8
55.8
55.4
52.4
52.0
0.7
0.8
0.7
0.6
0.7
0.9
0.7
0.6
0.6
0.6
0.6
0.9
0.7
0.7
0.6
0.3
0.5
0.5
0.4
0.3
0.5
0.5
0.4
0.4
0.4
0.7
0.3
0.6
0.8
0.7
0.5
0.8
0.6
0.4
0.3
Points
R1
R2
3.30 1.64
3.30 1.66
3.30 1.68
3.30 1.72
3.30 1.76
3.30 1.80
3.30 1.84
3.30 1.88
3.30 1.92
3.30 1.96
3.30 2.00
3.30 2.04
3.30 2.08
3.30 2.12
3.30 2.16
3.30 2.20
3.30 2.25
3.30 2.30
3.30 2.35
3.30 2.40
3.30 2.45
3.30 2.50
3.30 2.55
3.30 2.60
3.30 2.65
3.30 2.70
3.30 2.80
3.30 2.90
3.30 3.00
3.30 3.10
3.30 3.20
3.30 3.30
3.30 3.40
3.30 3.50
3.30 3.60
Free energy
Case A
31.6 0.6
33.4 0.9
29.2 0.7
25.9 0.6
29.3 1.4
29.2 1.5
32.8 0.8
36.6 0.5
36.0 0.6
46.4 0.6
43.9 1.1
50.5 0.8
52.0 1.0
56.7 0.4
58.5 0.4
49.9 0.6
50.5 0.4
48.5 0.6
50.3 0.6
51.6 0.5
48.9 0.4
46.2 0.5
50.3 0.9
45.4 0.6
48.0 0.9
48.1 0.7
47.5 0.6
42.1 0.6
42.7 0.5
42.3 0.4
43.6 1.0
41.7 0.6
44.7 0.4
42.4 0.7
41.6 0.9
with ave+/-std (kcal/mol)
Case B
Case C
Case
76.2 0.5 28.6 0.8 3.5
73.6 0.5 25.8 0.9 3.1
71.3 0.5 28.7 0.9 2.7
67.4 0.5 24.9 1.0 2.4
64.2 0.6 29.0 0.4 3.0
61.6 0.6 29.1 0.5 4.1
59.6 0.5 34.3 1.0 5.7
57.8 0.5 31.0 0.9 7.5
56.5 0.5 31.8 0.6 9.5
55.5 0.5 24.3 0.8 11.7
54.5 0.5 38.4 0.9 13.9
53.9 0.5 47.5 0.5 16.3
53.3 0.5 50.5 0.5 18.8
52.6 0.5 50.8 1.1 21.1
52.1 0.5 50.3 0.4 23.3
51.9 0.5 49.4 0.7 25.4
51.5 0.5 47.8 0.5 27.8
51.2 0.4 49.1 0.6 30.4
50.9 0.4 51.9 0.6 32.8
50.8 0.4 46.2 0.4 34.7
50.4 0.4 50.9 0.5 36.7
50.4 0.4 52.5 0.7 39.1
50.5 0.4 45.8 0.7 41.0
50.4 0.4 47.1 0.3 42.4
50.1 0.4 44.9 0.8 44.2
49.9 0.4 47.1 0.6 45.7
49.9 0.3 48.3 0.5 47.7
49.6 0.3 48.6 0.4 48.9
49.3 0.3 43.9 0.6 49.6
48.5 0.3 46.9 0.8 50.2
47.7 0.3 49.1 0.6 50.6
47.3 0.3 45.1 0.5 51.1
46.9 0.3 48.3 0.7 51.6
46.8 0.3 46.5 0.9 52.0
46.8 0.2 44.2 0.9 52.4
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
30.5
31.8
28.4
25.2
27.9
28.2
31.9
35.6
35.7
45.9
43.1
49.8
50.9
55.6
58.1
48.5
49.4
47.9
48.9
51.1
48.2
45.3
49.8
45.0
47.3
47.6
47.3
41.7
42.1
42.7
42.7
41.4
44.6
42.4
41.6
75.4
72.8
70.6
66.8
63.8
61.5
59.5
57.6
56.2
55.1
54.3
54.0
53.5
53.0
52.6
52.4
52.2
51.8
51.5
51.3
51.2
51.1
50.9
50.6
50.5
50.6
50.7
50.0
49.2
48.7
48.3
47.8
47.6
47.3
46.9
S26
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.6
1.0
0.8
0.5
1.5
1.4
0.7
0.6
0.6
0.6
1.2
0.7
1.1
0.5
0.4
0.6
0.4
0.6
0.6
0.5
0.4
0.5
0.8
0.6
1.0
0.6
0.6
0.7
0.5
0.5
1.0
0.5
0.5
0.8
1.0
0.8
0.8
0.8
0.8
0.8
0.9
0.9
0.9
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.6
0.5
0.5
0.4
0.3
0.3
27.0
25.0
27.3
23.9
28.0
28.4
33.2
30.6
30.8
23.4
37.8
46.9
50.0
50.2
49.3
48.4
46.9
47.9
51.8
45.0
50.4
52.4
44.8
46.7
44.4
46.4
47.8
49.0
43.0
46.8
48.8
44.9
48.3
46.4
44.2
0.9
0.9
1.0
1.1
0.4
0.5
1.1
1.1
0.7
0.9
0.9
0.6
0.5
1.1
0.4
0.7
0.5
0.7
0.6
0.4
0.5
0.8
0.7
0.4
0.8
0.6
0.5
0.5
0.7
0.8
0.7
0.5
0.7
0.9
0.9
1.9
1.4
1.1
1.0
1.6
2.9
4.4
6.1
8.2
10.5
12.9
15.5
17.9
20.2
22.6
24.7
27.3
29.7
32.2
34.4
36.4
38.4
40.4
41.9
43.5
44.8
46.8
48.9
50.6
51.9
52.7
53.3
53.9
54.4
54.5
D
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.8
0.8
0.9
0.9
1.0
1.0
Case
3.7
3.2
2.8
2.7
3.3
4.3
5.8
7.7
9.4
11.4
13.7
15.8
18.2
20.7
22.9
25.1
27.9
30.5
32.9
35.6
37.7
39.6
41.3
42.8
44.4
45.5
47.1
49.7
50.9
51.7
53.2
54.3
55.2
55.6
55.8
E
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.6
0.5
0.6
0.5
0.5
0.5
0.5
Case
3.8
3.1
2.7
2.6
3.1
4.1
5.7
7.5
9.5
11.4
13.5
15.9
18.5
21.1
23.2
25.2
28.0
30.7
32.9
34.9
37.0
38.8
40.4
42.0
43.2
44.3
46.0
47.5
49.2
50.3
51.5
52.5
52.9
53.2
53.5
F
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.2
0.3
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.9
0.9
1.0
0.9
0.9
1.0
0.9
0.9
1.2
0.7
0.5
0.8
1.5
2.9
4.3
6.0
8.0
10.3
12.5
14.8
17.1
19.4
21.7
23.9
26.5
29.4
31.9
34.1
36.2
38.1
39.9
41.4
42.9
44.6
48.1
50.1
52.0
53.0
53.8
54.5
55.0
55.8
56.4
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.8
0.8
0.8
0.8
0.9
2.8
1.9
1.5
1.9
2.3
3.3
4.8
6.8
8.8
10.7
13.0
15.3
17.7
20.2
22.5
24.5
27.3
29.8
32.0
34.3
36.8
38.4
40.0
41.7
43.2
43.6
45.7
47.1
48.8
49.6
51.7
51.9
52.7
53.1
53.4
0.3
0.3
0.2
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.1
0.2
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.4
0.5
0.4
0.4
0.4
0.4
0.4
0.4
Points
R1
R2
2.20 1.64
2.20 1.66
2.20 1.68
2.20 1.72
2.20 1.76
2.20 1.80
2.20 1.84
2.20 1.88
2.20 1.92
2.20 1.96
2.20 2.00
2.20 2.04
2.20 2.08
2.20 2.12
2.20 2.16
2.20 2.20
2.20 2.25
2.20 2.30
2.20 2.35
2.20 2.40
2.20 2.45
2.20 2.50
2.20 2.55
2.20 2.60
2.20 2.65
2.20 2.70
2.20 2.80
2.20 2.90
2.20 3.00
2.20 3.10
2.20 3.20
2.20 3.30
2.20 3.40
2.20 3.50
2.20 3.60
Free energy
Case A
52.2 0.3
50.1 0.4
50.5 0.2
48.1 0.2
47.2 0.3
47.2 0.2
48.0 0.3
49.0 0.4
49.3 0.3
50.0 0.3
52.6 0.2
51.5 0.2
54.2 0.3
53.6 0.3
52.0 0.2
48.8 0.4
46.1 0.2
44.9 0.2
43.4 0.4
42.3 0.2
40.4 0.2
37.5 0.2
35.6 0.3
33.1 0.3
33.4 0.4
31.4 0.4
29.7 0.4
24.3 0.2
25.1 0.4
22.8 0.4
20.7 0.5
23.3 0.4
21.3 0.4
20.4 0.5
20.5 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
84.8 1.1 47.6 0.4 37.1
83.8 1.1 45.9 0.5 36.3
82.4 1.1 45.4 0.4 35.6
79.3 0.7 43.8 0.2 34.7
75.8 0.7 42.3 0.3 34.5
72.2 0.7 43.2 0.3 35.0
69.4 0.9 43.5 0.3 36.0
66.4 0.8 43.3 0.4 37.1
63.9 0.8 45.1 0.4 38.4
61.5 0.8 46.2 0.3 39.8
59.3 0.8 46.9 0.1 41.3
57.3 0.8 48.3 0.3 42.9
55.5 0.8 48.7 0.3 44.5
53.7 0.8 49.9 0.3 46.1
52.1 0.7 49.6 0.2 47.5
50.3 0.7 45.6 0.3 48.9
48.1 0.8 44.4 0.3 50.9
46.2 0.7 42.3 0.2 52.8
44.2 0.7 41.1 0.3 54.1
42.3 0.7 39.3 0.3 55.1
40.7 0.7 39.4 0.3 56.3
39.0 0.6 36.9 0.4 57.6
37.4 0.6 34.5 0.4 58.0
36.0 0.6 32.6 0.3 58.4
34.6 0.5 31.9 0.3 59.2
33.3 0.5 30.7 0.3 59.9
30.8 0.6 28.3 0.3 59.2
28.1 0.6 25.2 0.4 57.8
25.8 0.6 25.2 0.4 57.1
24.4 0.5 24.1 0.3 55.9
23.2 0.4 24.1 0.4 54.3
22.3 0.4 22.9 0.5 53.6
21.7 0.3 23.0 0.6 52.8
21.3 0.3 21.8 0.8 52.0
20.8 0.2 22.2 0.8 51.7
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
52.2
50.4
50.5
47.6
47.5
47.8
48.6
49.9
50.5
51.2
53.7
52.7
55.5
54.9
53.4
49.7
47.3
46.2
44.6
44.0
42.2
39.5
37.5
34.9
35.4
33.7
31.9
26.5
27.2
24.7
23.1
25.8
23.8
22.7
23.0
83.9
81.7
79.1
74.4
70.7
67.5
64.5
62.0
59.7
57.7
55.8
54.2
52.6
51.1
49.9
48.8
47.4
45.5
43.5
42.2
40.9
39.4
38.0
36.5
35.1
33.8
31.7
29.9
28.2
27.0
25.6
24.6
24.0
23.6
23.4
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.2
0.4
0.3
0.3
0.4
0.3
0.3
0.4
0.2
0.3
0.3
0.2
0.3
0.3
0.2
0.4
0.3
0.2
0.4
0.2
0.2
0.3
0.3
0.3
0.4
0.4
0.4
0.2
0.4
0.5
0.5
0.4
0.4
0.5
0.6
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.6
0.6
0.6
0.5
0.4
0.3
0.2
0.2
0.2
0.2
47.2
46.0
45.0
44.5
42.6
43.3
44.0
44.1
46.0
47.4
48.3
49.6
50.5
51.6
51.2
46.9
46.0
44.0
42.7
40.8
41.5
39.2
36.4
34.3
33.8
32.9
30.4
27.7
27.5
26.9
26.3
25.0
25.6
24.6
24.9
0.4
0.5
0.4
0.3
0.3
0.2
0.3
0.4
0.4
0.3
0.1
0.3
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.6
0.6
0.8
0.8
36.4
35.6
35.0
34.3
34.1
34.5
35.4
36.4
37.8
39.0
40.5
42.0
43.4
45.1
47.0
48.6
50.6
52.0
52.9
53.7
54.4
55.1
55.3
55.5
55.6
55.4
54.3
52.7
51.2
50.0
49.1
47.8
46.4
45.0
44.0
D
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.2
0.2
0.2
0.4
0.5
0.6
0.6
0.7
0.7
0.6
0.6
0.5
Case
42.5
41.5
40.7
39.7
39.3
39.5
40.0
40.7
41.9
43.0
44.1
45.3
46.6
48.1
49.4
50.5
51.7
52.6
53.6
54.7
55.6
56.1
56.1
56.1
56.1
56.2
56.2
54.9
53.9
53.3
52.2
51.1
50.2
49.7
49.2
E
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.6
0.7
0.8
0.7
Case
42.2
40.4
41.0
40.5
39.1
39.4
39.9
38.6
41.0
42.3
44.8
47.0
49.0
48.4
44.7
51.2
53.0
53.0
51.9
52.2
56.6
55.5
54.3
56.6
55.6
54.6
57.0
55.8
56.5
52.2
56.7
55.8
55.3
52.7
52.3
F
0.7
0.7
0.7
0.6
0.8
0.9
0.8
0.6
0.6
0.6
0.6
0.9
0.7
0.7
0.6
0.3
0.5
0.5
0.4
0.4
0.5
0.5
0.4
0.5
0.4
0.7
0.3
0.6
0.8
0.7
0.5
0.8
0.6
0.4
0.3
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.6
0.7
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
39.7
38.7
38.0
36.9
36.5
36.7
37.5
38.2
39.2
40.5
41.5
42.6
44.2
45.5
46.6
48.0
49.3
50.4
51.3
52.2
52.7
53.2
53.6
53.6
53.6
53.5
53.1
52.3
51.6
50.8
49.6
48.9
48.4
47.8
47.3
0.6
0.6
0.6
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.6
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
40.2
37.8
38.8
37.7
36.7
36.5
37.3
36.0
38.7
40.4
42.6
45.1
46.6
46.8
43.5
49.7
51.6
51.4
50.4
51.0
55.6
54.3
53.3
55.5
54.8
53.9
56.4
55.2
56.3
52.2
56.6
55.8
55.4
53.0
52.8
0.7
0.5
0.7
0.6
0.8
0.9
0.8
0.6
0.6
0.6
0.6
0.9
0.7
0.7
0.7
0.3
0.5
0.5
0.4
0.4
0.5
0.4
0.4
0.5
0.4
0.7
0.3
0.6
0.8
0.8
0.5
0.8
0.6
0.5
0.3
Points
R1
R2
3.50 1.64
3.50 1.66
3.50 1.68
3.50 1.72
3.50 1.76
3.50 1.80
3.50 1.84
3.50 1.88
3.50 1.92
3.50 1.96
3.50 2.00
3.50 2.04
3.50 2.08
3.50 2.12
3.50 2.16
3.50 2.20
3.50 2.25
3.50 2.30
3.50 2.35
3.50 2.40
3.50 2.45
3.50 2.50
3.50 2.55
3.50 2.60
3.50 2.65
3.50 2.70
3.50 2.80
3.50 2.90
3.50 3.00
3.50 3.10
3.50 3.20
3.50 3.30
3.50 3.40
3.50 3.50
3.50 3.60
Free energy
Case A
29.9 0.7
30.9 1.0
27.7 0.6
25.0 0.6
27.0 1.4
27.7 1.4
31.4 0.7
35.1 0.6
35.4 0.6
45.6 0.8
42.9 1.2
48.8 0.6
49.8 1.2
54.8 0.6
57.6 0.3
47.6 0.6
48.4 0.4
46.8 0.7
47.4 0.7
50.5 0.5
47.1 0.6
44.6 0.5
49.0 0.8
44.6 0.7
46.3 1.0
47.0 0.7
47.2 0.6
41.1 0.7
42.1 0.6
42.8 0.5
41.4 1.2
41.3 0.5
44.7 0.5
42.1 0.8
41.4 1.0
with ave+/-std (kcal/mol)
Case B
Case C
Case
69.4 0.8 25.3 0.9 1.1
67.2 0.8 24.5 0.8 0.6
65.1 0.8 26.8 1.0 0.2
61.9 0.8 23.3 1.0 0.2
59.3 0.8 27.4 0.3 1.0
57.2 0.8 27.9 0.5 2.1
55.7 0.8 32.5 1.4 3.7
54.5 0.8 30.1 1.1 5.4
53.7 0.8 30.3 0.8 7.5
53.0 0.8 23.0 1.0 9.8
52.6 0.8 37.4 0.9 12.1
52.4 0.8 46.2 0.6 14.5
52.1 0.8 50.2 0.5 16.8
52.0 0.8 49.5 1.2 19.2
52.1 0.8 48.2 0.5 21.7
51.7 0.8 47.2 0.7 23.9
51.3 0.8 46.0 0.4 26.5
51.3 0.8 47.1 0.7 29.2
51.3 0.8 51.4 0.6 31.7
51.4 0.8 43.9 0.5 33.9
51.4 0.8 49.8 0.7 35.8
51.5 0.8 52.3 0.8 37.4
51.6 0.8 43.8 0.8 39.1
51.8 0.8 46.6 0.4 40.8
51.9 0.8 43.8 0.8 41.9
52.0 0.8 45.7 0.7 42.7
51.2 0.8 47.4 0.6 44.8
49.7 0.7 49.1 0.6 46.4
49.3 0.7 42.4 0.6 47.7
49.2 0.6 46.8 0.8 48.7
49.2 0.6 47.8 0.8 48.8
48.4 0.5 44.8 0.7 48.8
47.6 0.4 48.0 0.7 49.0
47.1 0.3 46.1 1.0 49.2
46.9 0.3 43.9 0.9 49.2
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
29.6
30.9
27.3
25.1
26.3
27.4
31.0
34.5
35.1
45.3
42.2
48.2
49.4
54.2
57.4
46.5
47.6
45.6
46.1
49.8
46.4
43.8
48.5
43.8
45.8
46.6
46.9
40.3
42.0
42.9
41.1
40.8
44.5
41.7
40.8
69.6
67.3
65.3
61.9
59.2
57.1
55.6
54.5
53.7
52.9
52.2
51.6
51.2
51.0
50.9
50.9
50.5
50.3
50.2
50.1
50.2
50.3
50.4
50.4
50.5
50.8
51.1
50.4
49.5
49.1
48.3
47.5
47.1
46.9
46.5
S27
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.6
1.0
0.7
0.8
1.5
1.4
0.9
0.6
0.6
0.9
1.2
0.7
1.3
0.7
0.3
0.6
0.4
0.7
0.7
0.6
0.6
0.5
0.7
0.7
1.0
0.7
0.6
0.7
0.7
0.5
1.2
0.5
0.5
0.9
1.1
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.7
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.5
0.5
0.5
0.5
0.4
0.4
0.3
23.5
24.5
26.4
23.1
26.3
27.6
32.1
29.9
29.8
22.4
37.1
45.3
50.4
48.6
47.6
46.2
44.9
46.2
50.8
43.0
48.9
51.9
43.1
46.4
43.2
45.0
46.9
48.8
42.1
46.6
46.8
44.7
47.9
45.4
43.6
1.0
0.9
1.0
1.1
0.4
0.6
1.4
1.2
0.8
1.0
1.0
0.6
0.6
1.1
0.5
0.8
0.4
0.7
0.6
0.6
0.8
0.8
0.7
0.4
0.8
0.8
0.7
0.6
0.6
0.8
0.8
0.6
0.8
1.0
0.9
0.7
0.1
-0.3
-0.2
0.6
2.0
3.4
5.2
7.2
9.3
11.4
13.5
15.9
18.3
20.7
22.9
25.5
27.9
30.4
32.6
34.7
37.2
39.0
40.7
42.2
43.5
46.7
48.4
49.5
50.9
52.2
53.1
54.2
55.0
55.2
D
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.8
0.7
0.7
0.7
0.6
0.6
0.7
0.7
0.7
0.8
0.9
0.9
0.9
Case
1.1
0.5
0.1
0.1
0.7
2.0
3.5
5.3
7.5
9.8
12.1
14.5
16.9
19.4
21.9
24.3
27.1
29.9
32.6
34.9
37.0
39.1
41.0
42.5
44.0
45.5
47.9
49.8
51.3
52.3
52.9
53.2
53.5
53.9
53.7
E
0.9
0.9
0.9
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.7
0.7
0.7
0.8
0.8
0.9
0.9
0.9
0.9
0.9
1.0
1.0
1.0
Case
2.2
1.5
0.7
1.3
1.9
2.6
4.2
5.9
8.8
10.2
12.6
14.8
17.1
20.0
21.9
24.1
26.8
29.2
31.5
33.5
36.4
37.9
39.8
41.6
43.2
43.2
45.5
46.8
48.4
49.2
51.5
51.8
52.2
52.9
53.2
F
0.4
0.5
0.4
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.2
0.2
0.3
0.3
0.3
0.3
0.2
0.3
0.3
0.4
0.4
0.4
0.3
0.4
0.6
0.5
0.4
0.4
0.4
0.4
0.4
0.5
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.7
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.9
0.8
0.9
1.0
1.0
0.9
0.9
0.9
0.7
0.1
-0.1
0.1
0.9
1.9
3.5
5.5
7.7
10.1
12.4
14.8
17.4
19.9
22.2
24.7
27.6
30.0
32.5
35.0
37.4
39.9
41.9
43.9
45.9
47.5
50.0
52.1
54.1
55.4
56.0
56.5
56.9
57.0
57.1
0.8
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.2
1.1
1.1
1.0
1.0
1.1
2.0
1.4
0.1
1.0
1.6
2.4
3.9
5.2
8.6
9.9
11.9
14.9
16.7
19.7
21.9
24.1
26.3
28.9
31.4
33.2
36.2
37.6
39.5
41.2
42.8
43.2
45.6
46.3
47.8
49.1
51.0
51.9
52.0
52.3
52.8
0.3
0.5
0.3
0.7
0.7
0.5
0.4
0.4
0.5
0.4
0.4
0.2
0.4
0.3
0.3
0.3
0.4
0.4
0.4
0.2
0.4
0.4
0.4
0.5
0.5
0.3
0.5
0.7
0.5
0.4
0.5
0.4
0.4
0.4
0.6
Points
R1
R2
2.30 1.64
2.30 1.66
2.30 1.68
2.30 1.72
2.30 1.76
2.30 1.80
2.30 1.84
2.30 1.88
2.30 1.92
2.30 1.96
2.30 2.00
2.30 2.04
2.30 2.08
2.30 2.12
2.30 2.16
2.30 2.20
2.30 2.25
2.30 2.30
2.30 2.35
2.30 2.40
2.30 2.45
2.30 2.50
2.30 2.55
2.30 2.60
2.30 2.65
2.30 2.70
2.30 2.80
2.30 2.90
2.30 3.00
2.30 3.10
2.30 3.20
2.30 3.30
2.30 3.40
2.30 3.50
2.30 3.60
Free energy
Case A
52.1 0.3
50.5 0.4
50.4 0.5
48.3 0.3
47.7 0.4
48.5 0.3
49.6 0.4
50.7 0.4
51.4 0.2
52.4 0.3
54.6 0.3
53.8 0.2
56.9 0.3
56.2 0.3
54.6 0.2
50.5 0.4
48.5 0.3
47.3 0.2
46.1 0.4
45.2 0.2
43.8 0.2
41.3 0.3
39.2 0.4
36.5 0.3
37.1 0.5
35.8 0.5
33.9 0.4
28.6 0.2
29.1 0.4
26.4 0.5
25.2 0.6
28.0 0.4
26.2 0.4
24.7 0.4
25.2 0.6
with ave+/-std (kcal/mol)
Case B
Case C
Case
81.7 0.5 46.9 0.4 34.9
80.6 0.5 46.3 0.4 33.9
79.0 0.5 44.5 0.4 33.2
73.5 0.5 45.1 0.3 32.4
70.0 0.5 42.7 0.3 32.5
66.7 0.5 43.6 0.2 32.9
63.6 0.5 44.6 0.3 33.5
61.0 0.5 44.9 0.4 34.2
59.0 0.5 46.8 0.4 35.1
57.2 0.4 48.6 0.3 36.3
55.4 0.4 49.6 0.1 37.6
53.9 0.4 51.1 0.3 38.7
52.5 0.4 52.0 0.4 40.0
51.1 0.5 53.0 0.4 41.5
49.8 0.5 52.7 0.3 42.9
48.6 0.5 48.2 0.3 44.1
47.1 0.5 47.2 0.3 45.4
45.7 0.5 45.6 0.3 46.9
44.5 0.5 43.9 0.3 48.3
43.3 0.5 42.3 0.3 49.2
42.4 0.5 43.3 0.3 49.7
41.0 0.5 41.1 0.4 50.3
39.4 0.4 38.0 0.3 51.0
38.2 0.4 36.0 0.4 51.3
37.1 0.4 35.8 0.3 51.4
36.0 0.4 35.0 0.3 51.3
33.6 0.3 32.6 0.4 50.8
32.1 0.3 29.9 0.4 50.1
30.7 0.3 29.7 0.4 49.5
29.2 0.3 29.3 0.4 48.5
27.9 0.3 28.7 0.4 47.7
26.9 0.2 27.3 0.6 46.9
26.2 0.2 27.9 0.6 46.5
25.9 0.2 27.3 0.7 45.9
25.9 0.2 27.3 0.7 45.2
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
52.1
50.6
50.7
48.5
48.0
48.3
49.0
51.5
51.9
53.4
55.4
54.9
58.3
57.2
55.9
51.4
49.5
48.2
47.4
46.3
45.1
42.6
40.6
38.0
38.9
37.4
35.8
30.6
31.1
28.3
27.5
29.8
28.4
26.7
27.1
89.5
86.5
83.8
79.1
75.0
71.7
68.8
66.2
63.9
61.9
60.1
58.2
56.6
55.1
53.7
52.3
50.7
49.4
47.7
46.2
44.8
43.3
41.9
40.6
39.5
38.2
35.8
34.1
32.7
31.8
31.0
30.2
29.6
28.8
28.1
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.3
0.5
0.6
0.3
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.4
0.4
0.2
0.4
0.2
0.2
0.3
0.4
0.2
0.5
0.5
0.4
0.2
0.4
0.5
0.5
0.4
0.4
0.4
0.6
1.0
1.0
1.0
1.0
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.9
0.8
0.8
0.8
0.7
0.7
0.7
0.7
0.7
0.6
0.7
0.7
0.7
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.3
0.2
0.2
46.9
44.7
44.5
45.6
42.8
44.4
45.0
45.3
47.4
47.8
50.6
52.0
53.4
54.4
53.9
49.2
48.1
47.0
45.0
43.3
44.8
42.6
39.6
37.7
37.6
36.7
34.7
32.0
31.6
31.5
30.9
29.4
30.2
29.9
29.6
0.4
0.4
0.4
0.3
0.3
0.2
0.3
0.4
0.4
0.3
0.2
0.3
0.3
0.4
0.3
0.3
0.3
0.3
0.4
0.2
0.3
0.5
0.3
0.3
0.4
0.3
0.4
0.4
0.4
0.4
0.5
0.6
0.6
0.8
0.7
32.5
31.6
30.9
30.3
30.2
30.4
31.2
32.3
33.5
34.9
36.5
38.2
39.6
40.9
42.4
43.8
45.3
46.7
47.4
47.9
48.8
49.7
50.2
50.4
50.5
50.5
50.0
49.2
48.2
47.4
46.7
45.9
45.5
45.2
44.5
D
0.1
0.2
0.2
0.1
0.1
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.4
0.3
0.4
0.4
0.4
0.3
0.4
0.4
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.4
0.5
0.6
0.5
0.5
0.5
0.6
0.6
Case
36.6
35.5
34.7
34.0
33.7
34.0
34.9
35.8
36.8
38.2
39.6
40.5
41.8
43.2
44.2
45.3
46.8
48.1
49.2
50.2
51.0
51.9
52.5
52.6
52.5
52.5
52.4
51.2
50.2
49.6
49.1
48.6
48.2
47.5
47.0
E
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.5
0.6
0.6
0.6
0.6
0.6
0.6
0.7
0.7
Case
37.7
35.0
35.9
34.9
33.9
33.8
34.5
33.7
36.4
38.2
40.3
43.2
44.3
45.4
42.3
48.1
50.2
50.1
49.2
49.9
54.5
53.2
52.5
54.7
54.0
53.1
56.1
55.1
56.1
52.2
56.6
55.6
55.4
53.3
53.0
F
0.7
0.5
0.7
0.6
0.7
0.9
0.8
0.6
0.6
0.6
0.6
0.8
0.7
0.7
0.7
0.4
0.5
0.5
0.4
0.4
0.5
0.4
0.4
0.5
0.4
0.6
0.3
0.6
0.8
0.8
0.5
0.8
0.6
0.4
0.3
0.2
0.2
0.2
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.2
0.2
0.2
0.3
0.3
0.3
0.3
0.3
0.3
0.3
0.4
0.4
0.4
0.4
0.5
0.5
0.6
0.6
0.6
0.6
0.7
0.8
34.7
33.7
33.0
32.1
31.7
31.9
32.6
33.6
35.3
36.7
38.1
39.6
40.9
42.2
43.5
44.7
46.3
47.6
48.8
49.8
50.7
51.5
51.9
52.0
52.0
51.6
50.5
50.1
49.2
48.5
47.9
47.2
46.2
45.3
44.6
0.6
0.5
0.5
0.5
0.5
0.4
0.4
0.4
0.4
0.4
0.3
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.5
0.5
0.4
0.4
0.4
0.4
0.3
0.3
0.3
0.4
0.4
0.6
0.6
0.6
0.5
34.7
32.7
33.3
32.0
31.1
31.2
32.1
31.7
34.2
36.0
38.3
40.6
42.0
43.8
41.1
46.5
48.5
48.8
48.1
48.9
53.4
52.2
51.5
54.0
53.3
52.4
55.7
54.8
56.0
52.1
56.5
55.4
55.4
53.6
53.3
0.7
0.5
0.7
0.6
0.7
0.9
0.8
0.6
0.6
0.6
0.6
0.8
0.6
0.6
0.6
0.4
0.5
0.5
0.4
0.4
0.5
0.4
0.4
0.5
0.4
0.6
0.3
0.6
0.8
0.7
0.5
0.7
0.6
0.5
0.3
Points
R1
R2
3.70 1.64
3.70 1.66
3.70 1.68
3.70 1.72
3.70 1.76
3.70 1.80
3.70 1.84
3.70 1.88
3.70 1.92
3.70 1.96
3.70 2.00
3.70 2.04
3.70 2.08
3.70 2.12
3.70 2.16
3.70 2.20
3.70 2.25
3.70 2.30
3.70 2.35
3.70 2.40
3.70 2.45
3.70 2.50
3.70 2.55
3.70 2.60
3.70 2.65
3.70 2.70
3.70 2.80
3.70 2.90
3.70 3.00
3.70 3.10
3.70 3.20
3.70 3.30
3.70 3.40
3.70 3.50
3.70 3.60
S28
Free energy
Case A
29.7 0.7
30.9 0.9
27.0 0.8
24.9 0.7
26.2 1.6
27.3 1.5
30.6 1.0
34.1 0.7
35.4 0.7
44.9 0.9
41.9 1.3
47.7 0.9
49.4 1.2
53.4 0.8
57.7 0.5
45.4 0.7
46.7 0.4
44.8 0.6
45.0 0.7
49.0 0.7
45.8 0.6
43.0 0.5
47.5 0.8
42.7 0.7
45.2 1.0
46.0 0.7
46.6 0.6
39.6 0.7
42.0 0.7
42.7 0.5
40.8 1.1
40.2 0.6
43.9 0.6
41.9 0.9
40.2 1.3
with ave+/-std (kcal/mol)
Case B
Case C
Case
71.4 0.8 22.7 1.1 0.9
68.9 0.8 25.0 1.0 0.3
66.5 0.8 26.0 1.1 0.0
62.8 0.8 23.4 1.3 0.2
59.9 0.8 25.4 0.4 0.6
57.6 0.8 27.5 0.6 1.7
55.7 0.7 31.4 1.4 3.4
54.0 0.7 29.9 1.2 5.4
52.8 0.7 29.1 0.7 7.7
52.0 0.8 21.9 1.1 9.7
51.3 0.8 37.2 0.9 12.0
50.9 0.8 44.8 0.7 14.4
50.5 0.7 50.4 0.6 16.9
50.3 0.8 47.7 1.1 19.5
50.0 0.8 46.9 0.5 22.0
49.6 0.8 45.4 0.8 24.4
49.2 0.8 44.0 0.5 27.2
49.3 0.8 45.8 0.9 29.9
49.3 0.8 50.1 0.7 32.4
49.2 0.8 42.4 0.6 35.0
49.1 0.8 47.9 0.9 37.2
48.9 0.7 51.3 0.8 39.1
48.8 0.7 42.1 0.6 41.0
48.7 0.7 46.0 0.4 42.7
48.8 0.7 42.6 0.8 44.1
48.8 0.7 44.4 0.9 45.3
49.0 0.6 46.3 0.8 47.9
49.1 0.6 48.4 0.7 50.1
48.5 0.7 41.9 0.6 51.3
47.9 0.6 46.4 0.9 52.2
47.7 0.6 46.4 0.8 52.7
47.3 0.6 44.7 0.6 53.2
46.7 0.6 47.6 0.9 53.6
46.3 0.6 44.9 1.0 54.2
46.0 0.5 43.7 0.9 54.7
D
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.8
0.8
0.8
0.7
0.7
0.7
0.8
0.7
0.7
0.7
0.7
0.7
0.7
0.7
0.7
Case
0.5
0.1
-0.1
-0.1
0.7
1.8
3.1
5.1
7.5
9.7
12.1
14.6
16.8
19.0
21.2
23.4
25.9
28.3
30.9
33.1
35.3
37.4
39.3
40.8
42.0
43.3
45.9
48.0
49.8
50.8
51.6
52.1
52.1
52.6
52.8
E
0.9
0.9
0.9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.2
1.3
1.3
1.4
1.4
1.4
1.4
1.5
1.5
Case
2.2
1.3
0.0
0.9
1.5
2.7
3.4
5.4
8.5
9.5
11.6
14.9
16.5
19.8
22.4
24.1
26.1
29.2
31.2
33.3
36.2
37.5
39.5
41.0
42.8
43.0
45.9
46.2
47.8
49.1
50.7
52.0
52.2
51.7
52.4
F
0.4
0.5
0.3
0.9
0.8
0.5
0.6
0.5
0.6
0.6
0.4
0.2
0.5
0.2
0.3
0.3
0.4
0.4
0.4
0.3
0.5
0.4
0.4
0.6
0.6
0.3
0.5
0.7
0.5
0.4
0.5
0.4
0.4
0.5
0.7
Table S5: The corrections to free energy from Fixman determinant for the first four
FES’s shown in Fig. 2. The corrections to free energy from the Fixman determinant are
estimated by −kB T lnh(det(z)−1/2 )ic , the last part in Eq.S(5). Its maximum is at point R1=3.70 Å,
R2=3.60 Å and its minimum is at point R1=1.64 Å, R2=1.64 Å. The difference between the maximum and the minimum is about 1 kcal/mol, which is very small compared to the total free energy.
Although the corrections from the Fixman determinant are small, we took them into account when
estimating the free energy surfaces. Cases A, B, C and D correspond to the FES’s in Fig. 2A, Fig.
2B, Fig. 2C and Fig. 2D, respectively. The simulation is divided into ten parts, over which ten
corrections are estimated for each point and the average and standard deviation are then evaluated.
Points
R1
R2
1.64 1.64
1.64 1.66
1.64 1.68
1.64 1.72
1.64 1.76
1.64 1.80
1.64 1.84
1.64 1.88
1.64 1.92
1.64 1.96
1.64 2.00
1.64 2.04
1.64 2.08
1.64 2.12
1.64 2.16
1.64 2.20
1.64 2.25
1.64 2.30
1.64 2.35
1.64 2.40
1.64 2.45
1.64 2.50
1.64 2.55
1.64 2.60
1.64 2.65
1.64 2.70
1.64 2.80
1.64 2.90
1.64 3.00
1.64 3.10
1.64 3.20
1.64 3.30
1.64 3.40
1.64 3.50
1.64 3.60
Corrections from
Case A
-2.756 0.0001
-2.749 0.0002
-2.741 0.0002
-2.727 0.0003
-2.713 0.0003
-2.700 0.0002
-2.687 0.0002
-2.674 0.0001
-2.662 0.0002
-2.650 0.0001
-2.625 0.0002
-2.614 0.0002
-2.602 0.0003
-2.591 0.0002
-2.582 0.0001
-2.569 0.0001
-2.638 0.0002
-2.556 0.0002
-2.542 0.0002
-2.530 0.0002
-2.518 0.0002
-2.506 0.0002
-2.493 0.0005
-2.482 0.0003
-2.469 0.0006
-2.459 0.0002
-2.436 0.0007
-2.415 0.0005
-2.373 0.0006
-2.353 0.0003
-2.394 0.0007
-2.335 0.0005
-2.317 0.0005
-2.294 0.0011
-2.277 0.0007
Fixman
Case B
-2.755
-2.748
-2.741
-2.727
-2.713
-2.700
-2.687
-2.674
-2.661
-2.649
-2.625
-2.613
-2.604
-2.593
-2.582
-2.569
-2.637
-2.556
-2.543
-2.529
-2.518
-2.505
-2.494
-2.482
-2.470
-2.459
-2.437
-2.415
-2.372
-2.351
-2.395
-2.334
-2.317
-2.278
-2.277
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0003 -2.755 0.0002 -2.755
0.0001 -2.748 0.0003 -2.748
0.0002 -2.740 0.0003 -2.741
0.0003 -2.728 0.0001 -2.727
0.0002 -2.714 0.0002 -2.714
0.0002 -2.701 0.0002 -2.700
0.0002 -2.687 0.0003 -2.687
0.0002 -2.675 0.0001 -2.674
0.0002 -2.662 0.0001 -2.662
0.0002 -2.650 0.0002 -2.650
0.0003 -2.626 0.0002 -2.626
0.0003 -2.614 0.0002 -2.615
0.0001 -2.603 0.0003 -2.603
0.0002 -2.591 0.0002 -2.591
0.0001 -2.582 0.0001 -2.582
0.0002 -2.569 0.0002 -2.569
0.0003 -2.637 0.0002 -2.638
0.0002 -2.555 0.0004 -2.554
0.0001 -2.542 0.0002 -2.542
0.0003 -2.531 0.0001 -2.529
0.0002 -2.518 0.0002 -2.518
0.0005 -2.506 0.0003 -2.506
0.0003 -2.493 0.0006 -2.493
0.0002 -2.482 0.0006 -2.482
0.0005 -2.470 0.0004 -2.468
0.0005 -2.459 0.0004 -2.459
0.0004 -2.436 0.0007 -2.437
0.0006 -2.413 0.0004 -2.417
0.0013 -2.368 0.0012 -2.360
0.0010 -2.348 0.0010 -2.349
0.0004 -2.393 0.0006 -2.386
0.0007 -2.333 0.0013 -2.338
0.0005 -2.314 0.0006 -2.320
0.0017 -2.295 0.0005 -2.305
0.0013 -2.274 0.0010 -2.279
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
1.68
-2.741
-2.733
-2.727
-2.713
-2.700
-2.686
-2.673
-2.660
-2.647
-2.635
-2.611
-2.599
-2.588
-2.579
-2.567
-2.554
-2.623
-2.541
-2.528
-2.516
-2.503
-2.490
-2.479
-2.468
-2.456
-2.443
-2.420
-2.402
-2.359
-2.340
-2.381
-2.319
-2.301
-2.282
-2.262
-2.741
-2.733
-2.726
-2.713
-2.699
-2.686
-2.673
-2.660
-2.647
-2.635
-2.612
-2.600
-2.589
-2.578
-2.568
-2.555
-2.623
-2.541
-2.527
-2.516
-2.504
-2.491
-2.479
-2.467
-2.457
-2.441
-2.423
-2.401
-2.354
-2.340
-2.380
-2.321
-2.300
-2.275
-2.264
0.0002
0.0002
0.0003
0.0002
0.0002
0.0002
0.0002
0.0004
0.0004
0.0002
0.0002
0.0001
0.0004
0.0003
0.0002
0.0001
0.0002
0.0003
0.0003
0.0003
0.0001
0.0003
0.0006
0.0006
0.0003
0.0009
0.0006
0.0006
0.0018
0.0007
0.0008
0.0009
0.0009
0.0010
0.0014
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0003
0.0003
0.0002
0.0003
0.0001
0.0002
0.0002
0.0002
0.0002
0.0002
0.0001
0.0004
0.0003
0.0001
0.0004
0.0003
0.0002
0.0002
0.0002
0.0002
0.0003
0.0004
0.0003
0.0003
0.0002
0.0005
0.0009
0.0003
0.0007
0.0005
0.0004
0.0009
0.0007
0.0008
0.0011
-2.741
-2.734
-2.727
-2.713
-2.699
-2.685
-2.673
-2.660
-2.647
-2.635
-2.611
-2.600
-2.588
-2.577
-2.568
-2.554
-2.624
-2.541
-2.529
-2.516
-2.504
-2.492
-2.479
-2.468
-2.456
-2.442
-2.422
-2.399
-2.360
-2.338
-2.377
-2.319
-2.292
-2.287
-2.263
0.0002
0.0001
0.0002
0.0002
0.0002
0.0004
0.0002
0.0001
0.0002
0.0002
0.0002
0.0001
0.0001
0.0002
0.0004
0.0002
0.0002
0.0002
0.0001
0.0002
0.0002
0.0001
0.0008
0.0003
0.0005
0.0012
0.0003
0.0006
0.0004
0.0005
0.0011
0.0011
0.0016
0.0008
0.0015
-2.739
-2.734
-2.726
-2.712
-2.699
-2.686
-2.672
-2.660
-2.647
-2.635
-2.611
-2.599
-2.589
-2.578
-2.567
-2.554
-2.623
-2.540
-2.527
-2.515
-2.502
-2.491
-2.479
-2.468
-2.455
-2.444
-2.424
-2.402
-2.361
-2.344
-2.382
-2.326
-2.307
-2.286
-2.274
0.0001
0.0002
0.0003
0.0002
0.0002
0.0002
0.0004
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0004
0.0003
0.0002
0.0004
0.0003
0.0008
0.0005
0.0005
0.0005
0.0006
0.0006
0.0012
0.0005
0.0005
0.0003
0.0024
Points
R1
R2
2.40 1.64
2.40 1.66
2.40 1.68
2.40 1.72
2.40 1.76
2.40 1.80
2.40 1.84
2.40 1.88
2.40 1.92
2.40 1.96
2.40 2.00
2.40 2.04
2.40 2.08
2.40 2.12
2.40 2.16
2.40 2.20
2.40 2.25
2.40 2.30
2.40 2.35
2.40 2.40
2.40 2.45
2.40 2.50
2.40 2.55
2.40 2.60
2.40 2.65
2.40 2.70
2.40 2.80
2.40 2.90
2.40 3.00
2.40 3.10
2.40 3.20
2.40 3.30
2.40 3.40
2.40 3.50
2.40 3.60
Corrections from
Case A
-2.530 0.0004
-2.522 0.0002
-2.515 0.0005
-2.501 0.0005
-2.487 0.0004
-2.474 0.0003
-2.461 0.0004
-2.448 0.0002
-2.436 0.0004
-2.423 0.0003
-2.399 0.0006
-2.387 0.0005
-2.376 0.0003
-2.365 0.0004
-2.357 0.0001
-2.411 0.0003
-2.343 0.0003
-2.330 0.0001
-2.316 0.0004
-2.304 0.0003
-2.291 0.0003
-2.279 0.0003
-2.267 0.0005
-2.254 0.0008
-2.242 0.0005
-2.232 0.0008
-2.211 0.0005
-2.191 0.0003
-2.148 0.0006
-2.165 0.0006
-2.116 0.0015
-2.105 0.0007
-2.088 0.0006
-2.074 0.0005
-2.060 0.0023
Fixman
Case B
-2.530
-2.524
-2.515
-2.502
-2.489
-2.475
-2.462
-2.449
-2.437
-2.425
-2.401
-2.389
-2.379
-2.366
-2.355
-2.413
-2.343
-2.329
-2.316
-2.304
-2.292
-2.279
-2.268
-2.255
-2.243
-2.230
-2.206
-2.188
-2.142
-2.166
-2.126
-2.106
-2.087
-2.072
-2.053
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0001 -2.530 0.0003 -2.529
0.0001 -2.522 0.0003 -2.522
0.0003 -2.516 0.0002 -2.515
0.0002 -2.501 0.0003 -2.501
0.0001 -2.487 0.0003 -2.487
0.0003 -2.474 0.0005 -2.474
0.0003 -2.460 0.0003 -2.462
0.0002 -2.448 0.0004 -2.448
0.0003 -2.435 0.0006 -2.435
0.0003 -2.422 0.0006 -2.424
0.0004 -2.399 0.0004 -2.399
0.0002 -2.388 0.0005 -2.389
0.0001 -2.376 0.0004 -2.378
0.0003 -2.365 0.0003 -2.367
0.0007 -2.356 0.0001 -2.356
0.0002 -2.412 0.0004 -2.411
0.0002 -2.343 0.0002 -2.343
0.0005 -2.329 0.0002 -2.329
0.0004 -2.317 0.0002 -2.316
0.0002 -2.305 0.0001 -2.303
0.0003 -2.292 0.0002 -2.292
0.0005 -2.279 0.0003 -2.280
0.0003 -2.268 0.0003 -2.268
0.0006 -2.257 0.0002 -2.257
0.0006 -2.244 0.0004 -2.246
0.0007 -2.229 0.0017 -2.234
0.0006 -2.206 0.0012 -2.212
0.0010 -2.190 0.0005 -2.191
0.0018 -2.149 0.0009 -2.151
0.0007 -2.168 0.0008 -2.171
0.0020 -2.130 0.0005 -2.130
0.0010 -2.107 0.0016 -2.115
0.0011 -2.083 0.0020 -2.098
0.0010 -2.070 0.0008 -2.077
0.0007 -2.051 0.0008 -2.063
0.0003
0.0003
0.0002
0.0002
0.0004
0.0002
0.0002
0.0004
0.0004
0.0003
0.0004
0.0003
0.0001
0.0002
0.0002
0.0002
0.0001
0.0004
0.0005
0.0002
0.0002
0.0002
0.0005
0.0003
0.0003
0.0004
0.0003
0.0003
0.0009
0.0005
0.0012
0.0002
0.0003
0.0012
0.0004
0.0002
0.0001
0.0003
0.0003
0.0002
0.0002
0.0002
0.0002
0.0004
0.0003
0.0002
0.0001
0.0004
0.0002
0.0002
0.0002
0.0003
0.0002
0.0002
0.0002
0.0004
0.0002
0.0005
0.0004
0.0004
0.0004
0.0003
0.0008
0.0013
0.0004
0.0003
0.0005
0.0005
0.0009
0.0004
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
2.45
-2.517
-2.511
-2.503
-2.490
-2.475
-2.461
-2.449
-2.436
-2.423
-2.411
-2.386
-2.374
-2.365
-2.354
-2.344
-2.398
-2.330
-2.318
-2.304
-2.292
-2.280
-2.268
-2.254
-2.242
-2.232
-2.220
-2.194
-2.176
-2.135
-2.156
-2.110
-2.096
-2.075
-2.056
-2.039
-2.518
-2.511
-2.504
-2.490
-2.476
-2.461
-2.450
-2.437
-2.424
-2.412
-2.388
-2.377
-2.366
-2.354
-2.343
-2.400
-2.330
-2.317
-2.305
-2.291
-2.278
-2.266
-2.255
-2.244
-2.231
-2.220
-2.198
-2.177
-2.134
-2.154
-2.113
-2.093
-2.072
-2.057
-2.032
0.0002
0.0003
0.0001
0.0003
0.0001
0.0006
0.0002
0.0005
0.0004
0.0002
0.0003
0.0004
0.0001
0.0003
0.0003
0.0002
0.0002
0.0003
0.0004
0.0003
0.0006
0.0008
0.0006
0.0005
0.0010
0.0005
0.0005
0.0007
0.0007
0.0014
0.0009
0.0010
0.0007
0.0020
0.0018
0.0002
0.0006
0.0003
0.0003
0.0003
0.0005
0.0003
0.0003
0.0004
0.0004
0.0003
0.0002
0.0003
0.0003
0.0003
0.0005
0.0003
0.0007
0.0002
0.0006
0.0004
0.0004
0.0003
0.0003
0.0003
0.0004
0.0003
0.0004
0.0006
0.0005
0.0002
0.0006
0.0006
0.0010
0.0010
S29
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0002
0.0003
0.0002
0.0004
0.0004
0.0002
0.0005
0.0004
0.0002
0.0006
0.0005
0.0004
0.0003
0.0002
0.0005
0.0002
0.0002
0.0003
0.0003
0.0003
0.0002
0.0006
0.0007
0.0006
0.0002
0.0008
0.0008
0.0008
0.0007
0.0016
0.0008
0.0008
0.0009
0.0013
-2.517
-2.509
-2.503
-2.488
-2.475
-2.462
-2.449
-2.436
-2.424
-2.411
-2.388
-2.376
-2.363
-2.352
-2.343
-2.399
-2.331
-2.318
-2.304
-2.293
-2.280
-2.268
-2.256
-2.243
-2.231
-2.220
-2.198
-2.172
-2.130
-2.157
-2.107
-2.087
-2.063
-2.056
-2.035
0.0004
0.0003
0.0002
0.0006
0.0003
0.0004
0.0003
0.0002
0.0003
0.0006
0.0002
0.0003
0.0008
0.0007
0.0003
0.0004
0.0002
0.0002
0.0004
0.0001
0.0002
0.0003
0.0002
0.0004
0.0006
0.0004
0.0004
0.0008
0.0012
0.0004
0.0010
0.0010
0.0009
0.0009
0.0010
-2.517
-2.509
-2.503
-2.488
-2.475
-2.461
-2.449
-2.435
-2.423
-2.411
-2.387
-2.376
-2.365
-2.353
-2.343
-2.399
-2.330
-2.316
-2.304
-2.291
-2.279
-2.267
-2.256
-2.244
-2.233
-2.221
-2.201
-2.178
-2.137
-2.158
-2.121
-2.101
-2.085
-2.064
-2.049
Points
R1
R2
1.72 1.64
1.72 1.66
1.72 1.68
1.72 1.72
1.72 1.76
1.72 1.80
1.72 1.84
1.72 1.88
1.72 1.92
1.72 1.96
1.72 2.00
1.72 2.04
1.72 2.08
1.72 2.12
1.72 2.16
1.72 2.20
1.72 2.25
1.72 2.30
1.72 2.35
1.72 2.40
1.72 2.45
1.72 2.50
1.72 2.55
1.72 2.60
1.72 2.65
1.72 2.70
1.72 2.80
1.72 2.90
1.72 3.00
1.72 3.10
1.72 3.20
1.72 3.30
1.72 3.40
1.72 3.50
1.72 3.60
Corrections from
Case A
-2.727 0.0003
-2.720 0.0002
-2.713 0.0003
-2.699 0.0003
-2.685 0.0003
-2.672 0.0002
-2.659 0.0002
-2.646 0.0001
-2.634 0.0002
-2.621 0.0003
-2.598 0.0002
-2.586 0.0003
-2.574 0.0002
-2.563 0.0002
-2.554 0.0002
-2.541 0.0001
-2.609 0.0001
-2.527 0.0004
-2.514 0.0002
-2.502 0.0002
-2.490 0.0002
-2.477 0.0003
-2.465 0.0004
-2.453 0.0005
-2.443 0.0003
-2.431 0.0002
-2.408 0.0004
-2.387 0.0003
-2.345 0.0005
-2.326 0.0006
-2.364 0.0012
-2.303 0.0005
-2.288 0.0002
-2.265 0.0015
-2.251 0.0010
Fixman
Case B
-2.727
-2.719
-2.712
-2.698
-2.685
-2.671
-2.659
-2.646
-2.633
-2.621
-2.597
-2.587
-2.576
-2.565
-2.553
-2.540
-2.609
-2.528
-2.515
-2.502
-2.490
-2.478
-2.466
-2.453
-2.443
-2.430
-2.410
-2.386
-2.346
-2.326
-2.366
-2.307
-2.288
-2.271
-2.242
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0003 -2.727 0.0004 -2.727
0.0002 -2.720 0.0002 -2.720
0.0003 -2.713 0.0003 -2.712
0.0002 -2.699 0.0002 -2.697
0.0003 -2.685 0.0001 -2.685
0.0002 -2.672 0.0003 -2.671
0.0002 -2.659 0.0002 -2.659
0.0002 -2.646 0.0002 -2.646
0.0003 -2.634 0.0002 -2.634
0.0002 -2.621 0.0001 -2.621
0.0003 -2.598 0.0002 -2.598
0.0001 -2.586 0.0002 -2.586
0.0001 -2.574 0.0002 -2.575
0.0001 -2.565 0.0001 -2.564
0.0003 -2.554 0.0000 -2.553
0.0002 -2.540 0.0002 -2.539
0.0004 -2.609 0.0002 -2.609
0.0002 -2.528 0.0001 -2.527
0.0002 -2.514 0.0003 -2.514
0.0001 -2.502 0.0002 -2.502
0.0002 -2.489 0.0005 -2.489
0.0001 -2.477 0.0005 -2.478
0.0003 -2.465 0.0002 -2.465
0.0003 -2.454 0.0004 -2.453
0.0002 -2.441 0.0007 -2.439
0.0006 -2.428 0.0010 -2.430
0.0003 -2.404 0.0010 -2.404
0.0003 -2.383 0.0010 -2.384
0.0004 -2.341 0.0014 -2.340
0.0005 -2.324 0.0007 -2.320
0.0004 -2.364 0.0006 -2.365
0.0005 -2.308 0.0007 -2.299
0.0007 -2.287 0.0007 -2.280
0.0011 -2.269 0.0006 -2.267
0.0020 -2.229 0.0005 -2.242
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
1.76
-2.713
-2.706
-2.699
-2.685
-2.672
-2.658
-2.645
-2.632
-2.620
-2.607
-2.584
-2.572
-2.560
-2.549
-2.538
-2.527
-2.596
-2.513
-2.501
-2.488
-2.476
-2.464
-2.452
-2.440
-2.427
-2.416
-2.393
-2.373
-2.330
-2.310
-2.351
-2.292
-2.275
-2.252
-2.237
-2.714
-2.706
-2.699
-2.685
-2.671
-2.658
-2.645
-2.632
-2.621
-2.609
-2.585
-2.574
-2.561
-2.551
-2.540
-2.527
-2.597
-2.514
-2.501
-2.488
-2.476
-2.463
-2.452
-2.439
-2.428
-2.416
-2.395
-2.373
-2.326
-2.311
-2.351
-2.293
-2.273
-2.255
-2.234
0.0002
0.0003
0.0001
0.0002
0.0002
0.0003
0.0003
0.0002
0.0001
0.0002
0.0001
0.0002
0.0004
0.0002
0.0000
0.0001
0.0001
0.0002
0.0001
0.0002
0.0002
0.0004
0.0005
0.0005
0.0005
0.0003
0.0004
0.0005
0.0006
0.0008
0.0006
0.0003
0.0008
0.0013
0.0014
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0002
0.0003
0.0002
0.0001
0.0002
0.0003
0.0002
0.0002
0.0003
0.0003
0.0002
0.0004
0.0002
0.0005
0.0002
0.0002
0.0002
0.0002
0.0003
0.0002
0.0003
0.0004
0.0005
0.0007
0.0005
0.0005
0.0005
0.0010
0.0013
0.0009
0.0005
0.0008
0.0013
0.0014
-2.713
-2.707
-2.700
-2.685
-2.671
-2.658
-2.646
-2.633
-2.620
-2.608
-2.583
-2.572
-2.561
-2.549
-2.540
-2.527
-2.595
-2.514
-2.501
-2.488
-2.476
-2.464
-2.452
-2.440
-2.426
-2.416
-2.391
-2.372
-2.333
-2.313
-2.350
-2.292
-2.272
-2.254
-2.236
0.0003
0.0002
0.0002
0.0002
0.0002
0.0002
0.0001
0.0002
0.0001
0.0001
0.0003
0.0003
0.0002
0.0003
0.0002
0.0002
0.0002
0.0002
0.0002
0.0002
0.0003
0.0003
0.0001
0.0002
0.0010
0.0007
0.0008
0.0006
0.0007
0.0008
0.0006
0.0007
0.0013
0.0005
0.0005
-2.713
-2.706
-2.699
-2.685
-2.672
-2.657
-2.645
-2.632
-2.620
-2.607
-2.584
-2.572
-2.561
-2.550
-2.540
-2.526
-2.596
-2.512
-2.500
-2.487
-2.475
-2.463
-2.450
-2.439
-2.429
-2.416
-2.397
-2.374
-2.334
-2.316
-2.354
-2.298
-2.278
-2.261
-2.246
0.0002
0.0002
0.0003
0.0007
0.0002
0.0004
0.0003
0.0002
0.0003
0.0002
0.0002
0.0001
0.0002
0.0002
0.0003
0.0003
0.0002
0.0001
0.0001
0.0002
0.0003
0.0002
0.0003
0.0004
0.0007
0.0003
0.0010
0.0007
0.0011
0.0023
0.0010
0.0006
0.0021
0.0004
0.0015
Points
R1
R2
2.50 1.64
2.50 1.66
2.50 1.68
2.50 1.72
2.50 1.76
2.50 1.80
2.50 1.84
2.50 1.88
2.50 1.92
2.50 1.96
2.50 2.00
2.50 2.04
2.50 2.08
2.50 2.12
2.50 2.16
2.50 2.20
2.50 2.25
2.50 2.30
2.50 2.35
2.50 2.40
2.50 2.45
2.50 2.50
2.50 2.55
2.50 2.60
2.50 2.65
2.50 2.70
2.50 2.80
2.50 2.90
2.50 3.00
2.50 3.10
2.50 3.20
2.50 3.30
2.50 3.40
2.50 3.50
2.50 3.60
Corrections from
Case A
-2.505 0.0003
-2.499 0.0002
-2.491 0.0004
-2.477 0.0004
-2.463 0.0005
-2.449 0.0006
-2.437 0.0003
-2.423 0.0004
-2.412 0.0005
-2.400 0.0003
-2.375 0.0005
-2.362 0.0005
-2.352 0.0006
-2.342 0.0002
-2.332 0.0002
-2.387 0.0003
-2.318 0.0002
-2.306 0.0001
-2.292 0.0003
-2.278 0.0006
-2.268 0.0002
-2.256 0.0001
-2.243 0.0004
-2.232 0.0004
-2.217 0.0011
-2.209 0.0004
-2.186 0.0004
-2.164 0.0006
-2.121 0.0008
-2.143 0.0013
-2.089 0.0018
-2.083 0.0005
-2.060 0.0008
-2.048 0.0011
-2.031 0.0007
Fixman
Case B
-2.507
-2.499
-2.492
-2.478
-2.464
-2.451
-2.438
-2.425
-2.413
-2.401
-2.377
-2.365
-2.354
-2.342
-2.332
-2.388
-2.319
-2.305
-2.291
-2.279
-2.267
-2.255
-2.244
-2.232
-2.215
-2.207
-2.187
-2.166
-2.124
-2.141
-2.099
-2.081
-2.053
-2.051
-2.025
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0002 -2.504 0.0005 -2.505
0.0002 -2.498 0.0004 -2.497
0.0002 -2.491 0.0002 -2.491
0.0002 -2.476 0.0004 -2.477
0.0001 -2.463 0.0003 -2.463
0.0001 -2.450 0.0003 -2.448
0.0002 -2.436 0.0005 -2.437
0.0003 -2.424 0.0002 -2.424
0.0002 -2.411 0.0002 -2.411
0.0002 -2.400 0.0003 -2.400
0.0001 -2.375 0.0004 -2.377
0.0003 -2.363 0.0006 -2.364
0.0001 -2.350 0.0005 -2.352
0.0004 -2.339 0.0005 -2.342
0.0001 -2.331 0.0004 -2.329
0.0002 -2.385 0.0006 -2.388
0.0002 -2.318 0.0005 -2.318
0.0005 -2.305 0.0005 -2.305
0.0004 -2.293 0.0000 -2.293
0.0004 -2.280 0.0001 -2.280
0.0002 -2.266 0.0006 -2.267
0.0005 -2.254 0.0008 -2.256
0.0004 -2.243 0.0003 -2.242
0.0005 -2.232 0.0003 -2.231
0.0015 -2.221 0.0005 -2.221
0.0005 -2.207 0.0008 -2.210
0.0008 -2.180 0.0010 -2.187
0.0005 -2.162 0.0011 -2.168
0.0007 -2.126 0.0004 -2.127
0.0010 -2.141 0.0007 -2.145
0.0008 -2.102 0.0006 -2.109
0.0014 -2.084 0.0009 -2.088
0.0009 -2.056 0.0014 -2.069
0.0008 -2.037 0.0028 -2.057
0.0008 -2.024 0.0006 -2.039
0.0002
0.0005
0.0003
0.0003
0.0003
0.0004
0.0005
0.0004
0.0004
0.0002
0.0002
0.0005
0.0005
0.0004
0.0007
0.0003
0.0002
0.0004
0.0001
0.0001
0.0004
0.0002
0.0006
0.0006
0.0003
0.0003
0.0007
0.0005
0.0003
0.0010
0.0006
0.0006
0.0008
0.0001
0.0005
0.0003
0.0003
0.0002
0.0003
0.0003
0.0003
0.0002
0.0003
0.0003
0.0004
0.0004
0.0004
0.0002
0.0001
0.0002
0.0002
0.0003
0.0005
0.0004
0.0005
0.0002
0.0004
0.0007
0.0003
0.0003
0.0005
0.0003
0.0011
0.0005
0.0003
0.0006
0.0004
0.0008
0.0009
0.0003
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
2.55
-2.493
-2.487
-2.479
-2.465
-2.452
-2.438
-2.425
-2.412
-2.399
-2.388
-2.364
-2.350
-2.342
-2.330
-2.320
-2.374
-2.307
-2.292
-2.279
-2.268
-2.255
-2.244
-2.231
-2.220
-2.207
-2.197
-2.173
-2.152
-2.108
-2.134
-2.080
-2.072
-2.050
-2.030
-2.018
-2.495
-2.487
-2.480
-2.467
-2.453
-2.439
-2.426
-2.414
-2.401
-2.389
-2.365
-2.353
-2.342
-2.331
-2.320
-2.377
-2.307
-2.294
-2.279
-2.267
-2.255
-2.243
-2.231
-2.219
-2.208
-2.196
-2.172
-2.152
-2.104
-2.132
-2.089
-2.073
-2.049
-2.037
-2.014
0.0001
0.0002
0.0001
0.0001
0.0002
0.0002
0.0002
0.0001
0.0001
0.0001
0.0002
0.0002
0.0002
0.0002
0.0003
0.0001
0.0002
0.0001
0.0005
0.0006
0.0004
0.0006
0.0005
0.0004
0.0003
0.0005
0.0007
0.0007
0.0004
0.0004
0.0015
0.0005
0.0008
0.0007
0.0013
0.0002
0.0003
0.0007
0.0004
0.0002
0.0003
0.0004
0.0003
0.0006
0.0005
0.0004
0.0003
0.0005
0.0005
0.0004
0.0004
0.0003
0.0003
0.0006
0.0004
0.0002
0.0007
0.0004
0.0003
0.0007
0.0007
0.0003
0.0004
0.0004
0.0005
0.0003
0.0004
0.0011
0.0016
0.0009
S30
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0005
0.0002
0.0003
0.0004
0.0003
0.0004
0.0004
0.0006
0.0004
0.0003
0.0004
0.0007
0.0003
0.0003
0.0003
0.0006
0.0002
0.0006
0.0005
0.0002
0.0005
0.0002
0.0006
0.0004
0.0005
0.0005
0.0005
0.0007
0.0008
0.0007
0.0022
0.0010
0.0019
0.0007
0.0010
-2.494
-2.487
-2.480
-2.463
-2.452
-2.438
-2.425
-2.412
-2.398
-2.387
-2.363
-2.352
-2.340
-2.328
-2.320
-2.375
-2.307
-2.293
-2.281
-2.268
-2.256
-2.244
-2.233
-2.220
-2.206
-2.197
-2.176
-2.150
-2.112
-2.126
-2.091
-2.060
-2.044
-2.037
-2.009
0.0002
0.0002
0.0002
0.0004
0.0003
0.0003
0.0004
0.0004
0.0005
0.0006
0.0003
0.0003
0.0005
0.0006
0.0001
0.0007
0.0003
0.0003
0.0002
0.0004
0.0002
0.0004
0.0002
0.0004
0.0013
0.0005
0.0006
0.0010
0.0011
0.0013
0.0003
0.0019
0.0015
0.0008
0.0011
-2.493
-2.486
-2.478
-2.465
-2.452
-2.438
-2.425
-2.411
-2.399
-2.387
-2.363
-2.352
-2.340
-2.329
-2.317
-2.376
-2.305
-2.292
-2.279
-2.266
-2.255
-2.241
-2.230
-2.221
-2.207
-2.196
-2.176
-2.154
-2.116
-2.135
-2.096
-2.079
-2.058
-2.039
-2.025
Points
R1
R2
1.80 1.64
1.80 1.66
1.80 1.68
1.80 1.72
1.80 1.76
1.80 1.80
1.80 1.84
1.80 1.88
1.80 1.92
1.80 1.96
1.80 2.00
1.80 2.04
1.80 2.08
1.80 2.12
1.80 2.16
1.80 2.20
1.80 2.25
1.80 2.30
1.80 2.35
1.80 2.40
1.80 2.45
1.80 2.50
1.80 2.55
1.80 2.60
1.80 2.65
1.80 2.70
1.80 2.80
1.80 2.90
1.80 3.00
1.80 3.10
1.80 3.20
1.80 3.30
1.80 3.40
1.80 3.50
1.80 3.60
Corrections from
Case A
-2.700 0.0002
-2.693 0.0002
-2.686 0.0002
-2.672 0.0002
-2.658 0.0002
-2.645 0.0003
-2.631 0.0003
-2.619 0.0002
-2.606 0.0001
-2.595 0.0002
-2.570 0.0002
-2.558 0.0003
-2.547 0.0003
-2.538 0.0003
-2.527 0.0002
-2.514 0.0001
-2.582 0.0002
-2.500 0.0002
-2.488 0.0001
-2.475 0.0003
-2.461 0.0005
-2.450 0.0004
-2.438 0.0005
-2.425 0.0008
-2.413 0.0006
-2.404 0.0004
-2.380 0.0006
-2.358 0.0006
-2.310 0.0017
-2.299 0.0007
-2.340 0.0009
-2.280 0.0007
-2.260 0.0008
-2.243 0.0010
-2.223 0.0006
Fixman
Case B
-2.699
-2.693
-2.686
-2.670
-2.658
-2.645
-2.631
-2.619
-2.606
-2.594
-2.572
-2.560
-2.547
-2.537
-2.527
-2.513
-2.584
-2.500
-2.487
-2.475
-2.463
-2.449
-2.438
-2.426
-2.416
-2.404
-2.380
-2.360
-2.317
-2.298
-2.339
-2.268
-2.259
-2.230
-2.221
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0005 -2.700 0.0002 -2.700
0.0002 -2.693 0.0001 -2.692
0.0003 -2.687 0.0001 -2.685
0.0004 -2.672 0.0003 -2.671
0.0002 -2.658 0.0001 -2.658
0.0002 -2.645 0.0002 -2.645
0.0002 -2.632 0.0002 -2.632
0.0003 -2.619 0.0001 -2.619
0.0002 -2.607 0.0002 -2.606
0.0003 -2.595 0.0001 -2.592
0.0002 -2.570 0.0002 -2.571
0.0002 -2.558 0.0002 -2.559
0.0003 -2.547 0.0003 -2.547
0.0004 -2.536 0.0002 -2.536
0.0001 -2.527 0.0001 -2.525
0.0004 -2.513 0.0002 -2.511
0.0002 -2.581 0.0003 -2.582
0.0003 -2.500 0.0002 -2.499
0.0004 -2.487 0.0002 -2.485
0.0003 -2.475 0.0003 -2.473
0.0003 -2.462 0.0003 -2.462
0.0009 -2.450 0.0003 -2.450
0.0003 -2.437 0.0006 -2.438
0.0007 -2.426 0.0003 -2.426
0.0004 -2.415 0.0005 -2.415
0.0003 -2.404 0.0003 -2.404
0.0010 -2.378 0.0004 -2.384
0.0005 -2.359 0.0008 -2.352
0.0010 -2.316 0.0013 -2.322
0.0008 -2.288 0.0023 -2.294
0.0004 -2.328 0.0030 -2.340
0.0012 -2.272 0.0019 -2.272
0.0008 -2.258 0.0009 -2.266
0.0018 -2.243 0.0008 -2.250
0.0016 -2.220 0.0013 -2.228
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
1.84
-2.687
-2.680
-2.673
-2.659
-2.645
-2.632
-2.618
-2.606
-2.593
-2.581
-2.557
-2.546
-2.534
-2.523
-2.514
-2.500
-2.569
-2.487
-2.475
-2.462
-2.450
-2.437
-2.425
-2.414
-2.403
-2.390
-2.366
-2.341
-2.303
-2.286
-2.326
-2.266
-2.247
-2.229
-2.196
-2.687
-2.679
-2.673
-2.659
-2.645
-2.632
-2.619
-2.606
-2.593
-2.581
-2.558
-2.545
-2.536
-2.525
-2.514
-2.501
-2.569
-2.487
-2.475
-2.462
-2.449
-2.437
-2.425
-2.412
-2.400
-2.390
-2.367
-2.347
-2.304
-2.281
-2.326
-2.266
-2.247
-2.230
-2.203
0.0002
0.0002
0.0001
0.0002
0.0003
0.0002
0.0003
0.0003
0.0002
0.0001
0.0002
0.0003
0.0002
0.0003
0.0002
0.0002
0.0003
0.0001
0.0002
0.0003
0.0004
0.0002
0.0004
0.0010
0.0006
0.0005
0.0007
0.0004
0.0011
0.0020
0.0003
0.0005
0.0011
0.0019
0.0019
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0001
0.0002
0.0002
0.0002
0.0002
0.0003
0.0003
0.0002
0.0002
0.0003
0.0002
0.0003
0.0002
0.0003
0.0004
0.0003
0.0004
0.0002
0.0002
0.0001
0.0002
0.0002
0.0003
0.0003
0.0006
0.0013
0.0008
0.0012
0.0006
0.0006
0.0008
0.0011
0.0006
0.0022
-2.687
-2.680
-2.673
-2.659
-2.645
-2.632
-2.619
-2.606
-2.594
-2.582
-2.557
-2.545
-2.534
-2.523
-2.514
-2.501
-2.570
-2.487
-2.473
-2.461
-2.449
-2.437
-2.425
-2.414
-2.401
-2.392
-2.368
-2.340
-2.304
-2.283
-2.323
-2.257
-2.250
-2.211
-2.211
0.0001
0.0002
0.0001
0.0002
0.0002
0.0001
0.0003
0.0003
0.0001
0.0001
0.0001
0.0003
0.0003
0.0003
0.0002
0.0002
0.0003
0.0002
0.0005
0.0002
0.0003
0.0005
0.0003
0.0002
0.0007
0.0002
0.0005
0.0013
0.0008
0.0010
0.0014
0.0006
0.0006
0.0016
0.0007
-2.687
-2.680
-2.672
-2.659
-2.645
-2.632
-2.618
-2.606
-2.593
-2.582
-2.557
-2.546
-2.535
-2.524
-2.512
-2.499
-2.569
-2.486
-2.473
-2.460
-2.448
-2.435
-2.424
-2.411
-2.403
-2.391
-2.364
-2.346
-2.300
-2.289
-2.329
-2.268
-2.251
-2.237
-2.218
0.0001
0.0001
0.0004
0.0003
0.0002
0.0001
0.0002
0.0001
0.0002
0.0004
0.0003
0.0003
0.0003
0.0004
0.0003
0.0003
0.0003
0.0003
0.0005
0.0005
0.0004
0.0004
0.0004
0.0005
0.0003
0.0005
0.0002
0.0026
0.0005
0.0014
0.0008
0.0020
0.0005
0.0004
0.0007
Points
R1
R2
2.60 1.64
2.60 1.66
2.60 1.68
2.60 1.72
2.60 1.76
2.60 1.80
2.60 1.84
2.60 1.88
2.60 1.92
2.60 1.96
2.60 2.00
2.60 2.04
2.60 2.08
2.60 2.12
2.60 2.16
2.60 2.20
2.60 2.25
2.60 2.30
2.60 2.35
2.60 2.40
2.60 2.45
2.60 2.50
2.60 2.55
2.60 2.60
2.60 2.65
2.60 2.70
2.60 2.80
2.60 2.90
2.60 3.00
2.60 3.10
2.60 3.20
2.60 3.30
2.60 3.40
2.60 3.50
2.60 3.60
Corrections from
Case A
-2.482 0.0004
-2.474 0.0004
-2.467 0.0003
-2.453 0.0004
-2.437 0.0007
-2.426 0.0002
-2.412 0.0005
-2.400 0.0007
-2.388 0.0005
-2.377 0.0003
-2.351 0.0005
-2.339 0.0005
-2.328 0.0005
-2.318 0.0005
-2.309 0.0002
-2.363 0.0006
-2.295 0.0003
-2.282 0.0004
-2.267 0.0006
-2.256 0.0004
-2.245 0.0001
-2.232 0.0005
-2.219 0.0005
-2.206 0.0011
-2.191 0.0014
-2.183 0.0017
-2.163 0.0007
-2.140 0.0008
-2.097 0.0022
-2.120 0.0007
-2.078 0.0006
-2.056 0.0005
-2.040 0.0009
-2.016 0.0015
-2.005 0.0006
Fixman
Case B
-2.483
-2.475
-2.469
-2.455
-2.441
-2.428
-2.414
-2.401
-2.388
-2.377
-2.354
-2.342
-2.331
-2.320
-2.308
-2.365
-2.295
-2.282
-2.270
-2.257
-2.244
-2.232
-2.219
-2.207
-2.198
-2.185
-2.162
-2.141
-2.098
-2.116
-2.072
-2.058
-2.038
-2.010
-2.003
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0003 -2.483 0.0002 -2.482
0.0007 -2.474 0.0004 -2.474
0.0001 -2.467 0.0005 -2.466
0.0003 -2.453 0.0003 -2.453
0.0002 -2.439 0.0005 -2.439
0.0002 -2.426 0.0004 -2.426
0.0003 -2.414 0.0003 -2.412
0.0006 -2.401 0.0003 -2.400
0.0005 -2.389 0.0004 -2.387
0.0002 -2.376 0.0004 -2.375
0.0002 -2.353 0.0002 -2.351
0.0002 -2.341 0.0003 -2.341
0.0002 -2.329 0.0007 -2.329
0.0002 -2.318 0.0007 -2.318
0.0003 -2.309 0.0002 -2.308
0.0003 -2.364 0.0003 -2.364
0.0002 -2.296 0.0001 -2.294
0.0002 -2.282 0.0003 -2.281
0.0002 -2.269 0.0005 -2.269
0.0002 -2.257 0.0002 -2.256
0.0002 -2.244 0.0003 -2.242
0.0004 -2.232 0.0004 -2.230
0.0005 -2.221 0.0002 -2.221
0.0006 -2.207 0.0006 -2.209
0.0003 -2.194 0.0007 -2.196
0.0006 -2.185 0.0008 -2.185
0.0005 -2.160 0.0009 -2.164
0.0006 -2.136 0.0009 -2.144
0.0013 -2.092 0.0022 -2.104
0.0013 -2.120 0.0008 -2.119
0.0012 -2.076 0.0008 -2.086
0.0006 -2.062 0.0007 -2.067
0.0009 -2.019 0.0010 -2.048
0.0022 -2.021 0.0014 -2.025
0.0007 -1.993 0.0007 -2.014
0.0000
0.0005
0.0005
0.0005
0.0006
0.0004
0.0005
0.0003
0.0004
0.0004
0.0008
0.0002
0.0004
0.0005
0.0002
0.0003
0.0005
0.0005
0.0004
0.0002
0.0008
0.0006
0.0003
0.0005
0.0004
0.0007
0.0004
0.0003
0.0006
0.0005
0.0003
0.0005
0.0004
0.0005
0.0004
0.0002
0.0002
0.0002
0.0002
0.0003
0.0003
0.0004
0.0002
0.0003
0.0002
0.0003
0.0003
0.0003
0.0002
0.0002
0.0002
0.0002
0.0004
0.0003
0.0005
0.0006
0.0003
0.0005
0.0004
0.0002
0.0003
0.0016
0.0010
0.0011
0.0006
0.0003
0.0010
0.0009
0.0004
0.0009
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
2.65
-2.470
-2.464
-2.455
-2.441
-2.429
-2.413
-2.402
-2.387
-2.375
-2.366
-2.340
-2.328
-2.319
-2.305
-2.298
-2.352
-2.284
-2.271
-2.258
-2.245
-2.233
-2.219
-2.210
-2.196
-2.181
-2.175
-2.149
-2.129
-2.088
-2.111
-2.068
-2.052
-2.027
-2.001
-1.989
-2.472
-2.464
-2.457
-2.443
-2.430
-2.416
-2.404
-2.391
-2.378
-2.366
-2.342
-2.330
-2.319
-2.308
-2.296
-2.354
-2.284
-2.271
-2.258
-2.245
-2.233
-2.221
-2.208
-2.195
-2.186
-2.173
-2.147
-2.127
-2.083
-2.107
-2.067
-2.037
-2.026
-1.998
-1.980
0.0002
0.0002
0.0002
0.0002
0.0001
0.0003
0.0002
0.0001
0.0002
0.0001
0.0002
0.0004
0.0003
0.0004
0.0008
0.0001
0.0003
0.0001
0.0003
0.0007
0.0004
0.0004
0.0005
0.0007
0.0006
0.0008
0.0010
0.0021
0.0011
0.0011
0.0006
0.0007
0.0029
0.0011
0.0008
0.0003
0.0004
0.0004
0.0003
0.0006
0.0004
0.0003
0.0004
0.0007
0.0004
0.0004
0.0003
0.0003
0.0009
0.0004
0.0007
0.0008
0.0006
0.0004
0.0005
0.0009
0.0005
0.0005
0.0003
0.0005
0.0008
0.0002
0.0006
0.0004
0.0004
0.0003
0.0007
0.0005
0.0004
0.0004
S31
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0005
0.0004
0.0003
0.0006
0.0002
0.0004
0.0005
0.0006
0.0007
0.0002
0.0003
0.0005
0.0003
0.0005
0.0001
0.0007
0.0004
0.0004
0.0002
0.0004
0.0003
0.0006
0.0001
0.0003
0.0010
0.0003
0.0009
0.0006
0.0009
0.0005
0.0012
0.0018
0.0012
0.0025
0.0007
-2.471
-2.462
-2.456
-2.442
-2.428
-2.416
-2.402
-2.389
-2.377
-2.363
-2.342
-2.329
-2.317
-2.303
-2.297
-2.352
-2.284
-2.271
-2.256
-2.246
-2.233
-2.219
-2.209
-2.197
-2.185
-2.173
-2.150
-2.130
-2.087
-2.108
-2.064
-2.044
-2.016
-2.011
-1.984
0.0003
0.0005
0.0004
0.0002
0.0005
0.0003
0.0002
0.0004
0.0006
0.0006
0.0005
0.0004
0.0003
0.0005
0.0003
0.0007
0.0001
0.0002
0.0005
0.0001
0.0004
0.0009
0.0006
0.0005
0.0005
0.0006
0.0005
0.0007
0.0013
0.0008
0.0003
0.0011
0.0010
0.0024
0.0025
-2.470
-2.462
-2.454
-2.442
-2.428
-2.415
-2.402
-2.389
-2.376
-2.363
-2.339
-2.330
-2.318
-2.305
-2.295
-2.352
-2.281
-2.268
-2.257
-2.240
-2.227
-2.218
-2.208
-2.198
-2.185
-2.172
-2.154
-2.130
-2.093
-2.113
-2.075
-2.054
-2.038
-2.021
-2.005
Points
R1
R2
1.80 1.64
1.88 1.64
1.88 1.66
1.88 1.68
1.88 1.72
1.88 1.76
1.88 1.80
1.88 1.84
1.88 1.88
1.88 1.92
1.88 1.96
1.88 2.00
1.88 2.04
1.88 2.08
1.88 2.12
1.88 2.16
1.88 2.20
1.88 2.25
1.88 2.30
1.88 2.35
1.88 2.40
1.88 2.45
1.88 2.50
1.88 2.55
1.88 2.60
1.88 2.65
1.88 2.70
1.88 2.80
1.88 2.90
1.88 3.00
1.88 3.10
1.88 3.20
1.88 3.30
1.88 3.40
1.88 3.50
1.88 3.60
Corrections from
Case A
-2.700 0.0002
-2.675 0.0001
-2.667 0.0002
-2.660 0.0002
-2.646 0.0003
-2.633 0.0003
-2.619 0.0002
-2.606 0.0003
-2.593 0.0002
-2.580 0.0003
-2.568 0.0003
-2.544 0.0003
-2.533 0.0003
-2.521 0.0004
-2.510 0.0003
-2.501 0.0002
-2.488 0.0002
-2.556 0.0003
-2.474 0.0002
-2.462 0.0003
-2.450 0.0002
-2.437 0.0002
-2.425 0.0001
-2.412 0.0004
-2.400 0.0005
-2.389 0.0003
-2.375 0.0014
-2.356 0.0005
-2.330 0.0007
-2.295 0.0008
-2.273 0.0007
-2.314 0.0003
-2.256 0.0005
-2.237 0.0008
-2.197 0.0021
-2.198 0.0006
Fixman
Case B
-2.699
-2.674
-2.667
-2.660
-2.647
-2.632
-2.619
-2.606
-2.593
-2.580
-2.570
-2.546
-2.535
-2.523
-2.512
-2.501
-2.488
-2.558
-2.474
-2.461
-2.449
-2.436
-2.425
-2.413
-2.400
-2.389
-2.377
-2.353
-2.334
-2.293
-2.272
-2.312
-2.251
-2.235
-2.216
-2.196
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0005 -2.700 0.0002 -2.700
0.0003 -2.674 0.0002 -2.674
0.0003 -2.667 0.0002 -2.667
0.0002 -2.661 0.0002 -2.659
0.0001 -2.646 0.0002 -2.645
0.0003 -2.633 0.0001 -2.632
0.0001 -2.619 0.0001 -2.618
0.0003 -2.606 0.0003 -2.605
0.0003 -2.593 0.0002 -2.592
0.0003 -2.580 0.0002 -2.581
0.0002 -2.569 0.0002 -2.568
0.0001 -2.544 0.0003 -2.545
0.0001 -2.533 0.0004 -2.533
0.0001 -2.521 0.0002 -2.521
0.0002 -2.510 0.0005 -2.509
0.0004 -2.502 0.0001 -2.500
0.0002 -2.488 0.0001 -2.487
0.0002 -2.556 0.0003 -2.556
0.0003 -2.474 0.0003 -2.474
0.0003 -2.461 0.0003 -2.461
0.0002 -2.448 0.0004 -2.449
0.0004 -2.436 0.0002 -2.435
0.0003 -2.424 0.0005 -2.422
0.0003 -2.412 0.0003 -2.412
0.0003 -2.401 0.0004 -2.401
0.0005 -2.387 0.0012 -2.388
0.0008 -2.378 0.0004 -2.374
0.0011 -2.355 0.0006 -2.351
0.0005 -2.334 0.0011 -2.329
0.0003 -2.283 0.0009 -2.282
0.0008 -2.271 0.0005 -2.261
0.0008 -2.311 0.0012 -2.312
0.0006 -2.255 0.0007 -2.232
0.0007 -2.228 0.0008 -2.222
0.0011 -2.199 0.0013 -2.195
0.0008 -2.194 0.0010 -2.177
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
1.92
-2.662
-2.655
-2.647
-2.634
-2.620
-2.607
-2.593
-2.581
-2.568
-2.555
-2.532
-2.520
-2.508
-2.497
-2.487
-2.476
-2.544
-2.462
-2.449
-2.437
-2.424
-2.412
-2.399
-2.387
-2.377
-2.362
-2.341
-2.318
-2.280
-2.260
-2.299
-2.241
-2.223
-2.202
-2.186
-2.662
-2.654
-2.647
-2.633
-2.619
-2.606
-2.593
-2.582
-2.569
-2.557
-2.532
-2.522
-2.510
-2.499
-2.488
-2.475
-2.545
-2.461
-2.449
-2.436
-2.425
-2.412
-2.400
-2.389
-2.377
-2.366
-2.343
-2.320
-2.282
-2.252
-2.300
-2.241
-2.215
-2.202
-2.184
0.0003
0.0003
0.0003
0.0003
0.0004
0.0003
0.0003
0.0001
0.0003
0.0001
0.0003
0.0001
0.0003
0.0003
0.0003
0.0004
0.0001
0.0003
0.0004
0.0002
0.0002
0.0004
0.0003
0.0006
0.0005
0.0004
0.0012
0.0011
0.0005
0.0015
0.0010
0.0014
0.0017
0.0014
0.0010
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0002
0.0002
0.0002
0.0001
0.0002
0.0002
0.0002
0.0003
0.0003
0.0003
0.0002
0.0002
0.0003
0.0003
0.0001
0.0002
0.0003
0.0003
0.0003
0.0004
0.0004
0.0006
0.0005
0.0004
0.0010
0.0005
0.0011
0.0012
0.0006
0.0007
0.0012
0.0005
0.0016
0.0010
-2.662
-2.654
-2.648
-2.634
-2.620
-2.607
-2.594
-2.581
-2.568
-2.557
-2.532
-2.520
-2.509
-2.497
-2.488
-2.475
-2.544
-2.461
-2.449
-2.435
-2.423
-2.412
-2.399
-2.388
-2.375
-2.366
-2.341
-2.317
-2.280
-2.256
-2.279
-2.241
-2.223
-2.203
-2.166
0.0002
0.0003
0.0001
0.0002
0.0001
0.0002
0.0002
0.0002
0.0002
0.0002
0.0003
0.0003
0.0004
0.0003
0.0002
0.0001
0.0002
0.0002
0.0002
0.0004
0.0004
0.0002
0.0003
0.0005
0.0006
0.0003
0.0007
0.0014
0.0007
0.0006
0.0026
0.0009
0.0006
0.0007
0.0017
-2.662
-2.655
-2.648
-2.634
-2.619
-2.606
-2.593
-2.580
-2.568
-2.556
-2.532
-2.520
-2.509
-2.498
-2.488
-2.474
-2.545
-2.461
-2.448
-2.435
-2.422
-2.411
-2.400
-2.388
-2.376
-2.366
-2.340
-2.324
-2.285
-2.249
-2.304
-2.244
-2.226
-2.213
-2.184
0.0001
0.0003
0.0002
0.0002
0.0003
0.0001
0.0004
0.0004
0.0003
0.0003
0.0004
0.0002
0.0003
0.0004
0.0004
0.0002
0.0003
0.0004
0.0005
0.0004
0.0002
0.0005
0.0005
0.0006
0.0004
0.0006
0.0006
0.0018
0.0009
0.0019
0.0023
0.0012
0.0011
0.0014
0.0007
0.0003
Points
R1
R2
2.60 1.64
2.70 1.64
2.70 1.66
2.70 1.68
2.70 1.72
2.70 1.76
2.70 1.80
2.70 1.84
2.70 1.88
2.70 1.92
2.70 1.96
2.70 2.00
2.70 2.04
2.70 2.08
2.70 2.12
2.70 2.16
2.70 2.20
2.70 2.25
2.70 2.30
2.70 2.35
2.70 2.40
2.70 2.45
2.70 2.50
2.70 2.55
2.70 2.60
2.70 2.65
2.70 2.70
2.70 2.80
2.70 2.90
2.70 3.00
2.70 3.10
2.70 3.20
2.70 3.30
2.70 3.40
2.70 3.50
2.70 3.60
Corrections from
Case A
-2.482 0.0004
-2.458 0.0004
-2.450 0.0005
-2.443 0.0004
-2.428 0.0005
-2.415 0.0005
-2.401 0.0005
-2.389 0.0007
-2.375 0.0004
-2.364 0.0004
-2.355 0.0002
-2.330 0.0002
-2.315 0.0010
-2.306 0.0004
-2.296 0.0007
-2.287 0.0001
-2.341 0.0005
-2.273 0.0004
-2.260 0.0001
-2.242 0.0018
-2.234 0.0002
-2.220 0.0009
-2.209 0.0003
-2.197 0.0007
-2.183 0.0011
-2.172 0.0013
-2.165 0.0002
-2.142 0.0004
-2.116 0.0022
-2.078 0.0006
-2.099 0.0011
-2.053 0.0014
-2.024 0.0031
-2.013 0.0009
-1.981 0.0007
-1.975 0.0012
Fixman
Case B
-2.483
-2.461
-2.452
-2.446
-2.432
-2.418
-2.405
-2.391
-2.379
-2.366
-2.355
-2.330
-2.319
-2.308
-2.297
-2.286
-2.343
-2.273
-2.260
-2.246
-2.234
-2.220
-2.209
-2.198
-2.184
-2.174
-2.163
-2.141
-2.110
-2.071
-2.094
-2.051
-2.039
-1.994
-1.989
-1.983
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0003 -2.483 0.0002 -2.482
0.0001 -2.461 0.0001 -2.458
0.0006 -2.451 0.0005 -2.451
0.0003 -2.445 0.0004 -2.444
0.0002 -2.431 0.0004 -2.430
0.0002 -2.417 0.0005 -2.418
0.0002 -2.404 0.0004 -2.403
0.0004 -2.391 0.0004 -2.390
0.0002 -2.376 0.0007 -2.376
0.0003 -2.361 0.0012 -2.365
0.0002 -2.353 0.0004 -2.353
0.0005 -2.330 0.0002 -2.328
0.0003 -2.319 0.0003 -2.318
0.0001 -2.306 0.0008 -2.307
0.0002 -2.294 0.0009 -2.295
0.0003 -2.287 0.0001 -2.285
0.0003 -2.343 0.0002 -2.341
0.0004 -2.272 0.0003 -2.270
0.0001 -2.260 0.0003 -2.255
0.0006 -2.247 0.0002 -2.242
0.0004 -2.234 0.0003 -2.233
0.0008 -2.219 0.0010 -2.221
0.0006 -2.211 0.0002 -2.210
0.0007 -2.198 0.0004 -2.196
0.0010 -2.187 0.0003 -2.183
0.0005 -2.173 0.0007 -2.173
0.0008 -2.161 0.0003 -2.164
0.0007 -2.138 0.0012 -2.138
0.0007 -2.121 0.0003 -2.122
0.0017 -2.083 0.0003 -2.081
0.0008 -2.101 0.0004 -2.099
0.0010 -2.060 0.0006 -2.061
0.0014 -2.042 0.0008 -2.043
0.0006 -2.009 0.0007 -2.026
0.0010 -2.000 0.0011 -2.011
0.0013 -1.980 0.0013 -1.992
0.0000
0.0006
0.0007
0.0005
0.0004
0.0004
0.0005
0.0002
0.0006
0.0003
0.0005
0.0005
0.0003
0.0005
0.0005
0.0006
0.0005
0.0008
0.0009
0.0017
0.0004
0.0004
0.0002
0.0005
0.0004
0.0006
0.0003
0.0006
0.0004
0.0005
0.0008
0.0005
0.0006
0.0006
0.0002
0.0004
0.0002
0.0001
0.0002
0.0002
0.0003
0.0003
0.0003
0.0003
0.0002
0.0002
0.0004
0.0003
0.0003
0.0003
0.0003
0.0004
0.0003
0.0003
0.0004
0.0004
0.0006
0.0004
0.0003
0.0003
0.0007
0.0003
0.0009
0.0002
0.0002
0.0027
0.0004
0.0004
0.0006
0.0003
0.0017
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
2.80
-2.438
-2.430
-2.422
-2.406
-2.393
-2.383
-2.368
-2.354
-2.341
-2.328
-2.309
-2.295
-2.283
-2.275
-2.265
-2.319
-2.252
-2.237
-2.224
-2.213
-2.200
-2.187
-2.176
-2.164
-2.154
-2.141
-2.121
-2.094
-2.055
-2.078
-2.010
-2.012
-1.999
-1.973
-1.962
-2.438
-2.432
-2.424
-2.410
-2.396
-2.384
-2.370
-2.357
-2.344
-2.332
-2.309
-2.298
-2.287
-2.275
-2.264
-2.319
-2.250
-2.238
-2.223
-2.212
-2.200
-2.188
-2.176
-2.165
-2.151
-2.139
-2.117
-2.095
-2.058
-2.074
-2.035
-2.010
-1.984
-1.971
-1.959
0.0003
0.0002
0.0004
0.0003
0.0006
0.0002
0.0003
0.0005
0.0009
0.0004
0.0006
0.0001
0.0003
0.0002
0.0003
0.0010
0.0005
0.0002
0.0007
0.0005
0.0004
0.0006
0.0004
0.0003
0.0014
0.0010
0.0005
0.0011
0.0008
0.0010
0.0006
0.0007
0.0012
0.0012
0.0012
0.0007
0.0003
0.0003
0.0004
0.0003
0.0003
0.0004
0.0005
0.0007
0.0006
0.0009
0.0007
0.0005
0.0010
0.0008
0.0004
0.0007
0.0006
0.0007
0.0006
0.0007
0.0005
0.0009
0.0004
0.0007
0.0006
0.0004
0.0013
0.0008
0.0004
0.0005
0.0008
0.0011
0.0008
0.0007
S32
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0004
0.0005
0.0004
0.0010
0.0007
0.0003
0.0006
0.0004
0.0006
0.0009
0.0002
0.0008
0.0006
0.0003
0.0002
0.0006
0.0002
0.0007
0.0004
0.0003
0.0007
0.0002
0.0006
0.0005
0.0003
0.0004
0.0004
0.0011
0.0008
0.0005
0.0009
0.0012
0.0006
0.0010
0.0015
-2.437
-2.429
-2.423
-2.406
-2.395
-2.382
-2.369
-2.355
-2.344
-2.330
-2.306
-2.295
-2.284
-2.272
-2.262
-2.320
-2.252
-2.236
-2.222
-2.213
-2.200
-2.188
-2.176
-2.165
-2.153
-2.140
-2.121
-2.097
-2.060
-2.078
-2.039
-2.012
-1.993
-1.982
-1.952
0.0006
0.0011
0.0005
0.0007
0.0006
0.0003
0.0005
0.0005
0.0006
0.0005
0.0008
0.0006
0.0011
0.0011
0.0006
0.0007
0.0001
0.0005
0.0007
0.0002
0.0003
0.0003
0.0004
0.0003
0.0005
0.0007
0.0003
0.0011
0.0004
0.0006
0.0010
0.0012
0.0007
0.0019
0.0013
-2.435
-2.427
-2.422
-2.408
-2.393
-2.382
-2.368
-2.353
-2.342
-2.330
-2.305
-2.292
-2.286
-2.270
-2.259
-2.318
-2.246
-2.233
-2.222
-2.209
-2.197
-2.187
-2.173
-2.164
-2.151
-2.139
-2.120
-2.092
-2.059
-2.078
-2.032
-2.018
-1.999
-1.983
-1.958
Points
R1
R2
1.96 1.64
1.96 1.66
1.96 1.68
1.96 1.72
1.96 1.76
1.96 1.80
1.96 1.84
1.96 1.88
1.96 1.92
1.96 1.96
1.96 2.00
1.96 2.04
1.96 2.08
1.96 2.12
1.96 2.16
1.96 2.20
1.96 2.25
1.96 2.30
1.96 2.35
1.96 2.40
1.96 2.45
1.96 2.50
1.96 2.55
1.96 2.60
1.96 2.65
1.96 2.70
1.96 2.80
1.96 2.90
1.96 3.00
1.96 3.10
1.96 3.20
1.96 3.30
1.96 3.40
1.96 3.50
1.96 3.60
Corrections from
Case A
-2.650 0.0002
-2.642 0.0003
-2.635 0.0002
-2.621 0.0003
-2.607 0.0003
-2.595 0.0002
-2.581 0.0002
-2.568 0.0002
-2.556 0.0002
-2.544 0.0002
-2.520 0.0002
-2.508 0.0003
-2.497 0.0002
-2.485 0.0002
-2.476 0.0003
-2.463 0.0002
-2.531 0.0002
-2.449 0.0003
-2.437 0.0001
-2.424 0.0002
-2.412 0.0003
-2.400 0.0004
-2.388 0.0004
-2.376 0.0005
-2.362 0.0006
-2.353 0.0004
-2.329 0.0011
-2.305 0.0013
-2.262 0.0013
-2.246 0.0014
-2.289 0.0006
-2.227 0.0010
-2.209 0.0007
-2.188 0.0007
-2.169 0.0014
Fixman
Case B
-2.650
-2.643
-2.635
-2.622
-2.607
-2.594
-2.581
-2.570
-2.555
-2.545
-2.519
-2.510
-2.498
-2.487
-2.476
-2.463
-2.531
-2.450
-2.437
-2.425
-2.412
-2.399
-2.387
-2.376
-2.363
-2.353
-2.323
-2.311
-2.265
-2.247
-2.287
-2.226
-2.208
-2.192
-2.168
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0004 -2.650 0.0003 -2.650
0.0002 -2.642 0.0001 -2.642
0.0002 -2.636 0.0001 -2.635
0.0003 -2.622 0.0002 -2.620
0.0002 -2.608 0.0002 -2.607
0.0002 -2.595 0.0002 -2.594
0.0002 -2.581 0.0002 -2.581
0.0001 -2.568 0.0002 -2.568
0.0004 -2.556 0.0003 -2.555
0.0001 -2.544 0.0002 -2.543
0.0004 -2.519 0.0006 -2.520
0.0002 -2.508 0.0002 -2.508
0.0003 -2.496 0.0002 -2.497
0.0002 -2.485 0.0003 -2.486
0.0002 -2.477 0.0002 -2.475
0.0002 -2.463 0.0001 -2.461
0.0005 -2.530 0.0003 -2.531
0.0002 -2.450 0.0002 -2.448
0.0002 -2.437 0.0002 -2.435
0.0003 -2.424 0.0003 -2.422
0.0003 -2.412 0.0003 -2.412
0.0005 -2.400 0.0002 -2.398
0.0006 -2.388 0.0002 -2.388
0.0003 -2.377 0.0002 -2.376
0.0008 -2.364 0.0006 -2.364
0.0005 -2.353 0.0003 -2.354
0.0007 -2.330 0.0009 -2.332
0.0006 -2.309 0.0006 -2.312
0.0013 -2.266 0.0008 -2.272
0.0013 -2.251 0.0006 -2.249
0.0007 -2.282 0.0012 -2.292
0.0007 -2.227 0.0007 -2.234
0.0011 -2.205 0.0011 -2.216
0.0012 -2.191 0.0007 -2.200
0.0007 -2.162 0.0013 -2.183
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
2.00
-2.638
-2.630
-2.624
-2.610
-2.595
-2.582
-2.569
-2.556
-2.544
-2.532
-2.507
-2.496
-2.484
-2.474
-2.464
-2.520
-2.450
-2.437
-2.424
-2.412
-2.399
-2.388
-2.375
-2.364
-2.351
-2.341
-2.311
-2.294
-2.257
-2.233
-2.275
-2.217
-2.197
-2.183
-2.153
-2.639
-2.632
-2.625
-2.609
-2.597
-2.584
-2.571
-2.558
-2.546
-2.533
-2.509
-2.497
-2.486
-2.475
-2.464
-2.521
-2.451
-2.438
-2.425
-2.412
-2.400
-2.387
-2.375
-2.363
-2.350
-2.342
-2.319
-2.297
-2.254
-2.237
-2.277
-2.218
-2.196
-2.173
-2.162
0.0000
0.0001
0.0001
0.0003
0.0001
0.0001
0.0002
0.0002
0.0001
0.0001
0.0002
0.0001
0.0001
0.0003
0.0003
0.0001
0.0002
0.0001
0.0003
0.0002
0.0001
0.0004
0.0003
0.0005
0.0011
0.0004
0.0006
0.0008
0.0006
0.0005
0.0008
0.0005
0.0010
0.0028
0.0009
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0003
0.0001
0.0003
0.0004
0.0004
0.0002
0.0003
0.0003
0.0003
0.0003
0.0004
0.0002
0.0004
0.0003
0.0003
0.0003
0.0003
0.0005
0.0003
0.0005
0.0004
0.0006
0.0005
0.0005
0.0005
0.0019
0.0011
0.0008
0.0013
0.0007
0.0009
0.0014
0.0011
0.0015
-2.638
-2.631
-2.624
-2.609
-2.595
-2.582
-2.569
-2.556
-2.544
-2.531
-2.508
-2.496
-2.485
-2.473
-2.464
-2.520
-2.451
-2.438
-2.425
-2.412
-2.401
-2.386
-2.374
-2.364
-2.350
-2.339
-2.318
-2.300
-2.251
-2.235
-2.273
-2.215
-2.196
-2.177
-2.152
0.0002
0.0001
0.0003
0.0001
0.0003
0.0001
0.0002
0.0002
0.0002
0.0004
0.0002
0.0003
0.0002
0.0003
0.0002
0.0003
0.0002
0.0001
0.0002
0.0003
0.0002
0.0005
0.0009
0.0005
0.0006
0.0006
0.0007
0.0002
0.0015
0.0008
0.0010
0.0008
0.0008
0.0014
0.0007
-2.637
-2.631
-2.623
-2.609
-2.596
-2.583
-2.569
-2.556
-2.544
-2.532
-2.508
-2.497
-2.484
-2.474
-2.463
-2.519
-2.448
-2.437
-2.424
-2.412
-2.399
-2.387
-2.376
-2.363
-2.352
-2.342
-2.318
-2.292
-2.246
-2.230
-2.276
-2.215
-2.191
-2.168
-2.156
0.0001
0.0002
0.0002
0.0004
0.0002
0.0004
0.0004
0.0004
0.0005
0.0004
0.0003
0.0003
0.0002
0.0004
0.0002
0.0004
0.0004
0.0004
0.0004
0.0005
0.0003
0.0003
0.0002
0.0003
0.0006
0.0004
0.0003
0.0003
0.0003
0.0008
0.0001
0.0004
0.0004
0.0003
0.0005
Points
R1
R2
2.90 1.64
2.90 1.66
2.90 1.68
2.90 1.72
2.90 1.76
2.90 1.80
2.90 1.84
2.90 1.88
2.90 1.92
2.90 1.96
2.90 2.00
2.90 2.04
2.90 2.08
2.90 2.12
2.90 2.16
2.90 2.20
2.90 2.25
2.90 2.30
2.90 2.35
2.90 2.40
2.90 2.45
2.90 2.50
2.90 2.55
2.90 2.60
2.90 2.65
2.90 2.70
2.90 2.80
2.90 2.90
2.90 3.00
2.90 3.10
2.90 3.20
2.90 3.30
2.90 3.40
2.90 3.50
2.90 3.60
Corrections from
Case A
-2.415 0.0007
-2.407 0.0006
-2.400 0.0007
-2.387 0.0005
-2.368 0.0010
-2.358 0.0008
-2.343 0.0008
-2.332 0.0011
-2.321 0.0004
-2.312 0.0003
-2.287 0.0007
-2.275 0.0007
-2.264 0.0003
-2.254 0.0004
-2.243 0.0003
-2.293 0.0016
-2.230 0.0002
-2.216 0.0007
-2.203 0.0007
-2.192 0.0004
-2.179 0.0008
-2.167 0.0006
-2.156 0.0004
-2.144 0.0004
-2.132 0.0005
-2.122 0.0004
-2.096 0.0010
-2.076 0.0007
-2.033 0.0015
-2.057 0.0007
-2.018 0.0010
-2.000 0.0009
-1.976 0.0011
-1.954 0.0017
-1.935 0.0019
Fixman
Case B
-2.417
-2.411
-2.404
-2.390
-2.376
-2.363
-2.350
-2.337
-2.324
-2.312
-2.289
-2.276
-2.266
-2.254
-2.244
-2.300
-2.230
-2.217
-2.205
-2.191
-2.179
-2.168
-2.156
-2.144
-2.131
-2.120
-2.100
-2.079
-2.034
-2.051
-2.012
-1.995
-1.969
-1.936
-1.935
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0002 -2.414 0.0009 -2.415
0.0002 -2.408 0.0007 -2.406
0.0003 -2.401 0.0009 -2.399
0.0003 -2.388 0.0004 -2.386
0.0004 -2.373 0.0006 -2.372
0.0002 -2.356 0.0006 -2.358
0.0003 -2.346 0.0006 -2.345
0.0002 -2.334 0.0006 -2.333
0.0003 -2.319 0.0006 -2.320
0.0001 -2.308 0.0010 -2.308
0.0003 -2.287 0.0003 -2.284
0.0005 -2.273 0.0005 -2.275
0.0003 -2.258 0.0014 -2.264
0.0004 -2.254 0.0003 -2.249
0.0003 -2.243 0.0004 -2.243
0.0002 -2.296 0.0009 -2.295
0.0004 -2.231 0.0001 -2.226
0.0005 -2.218 0.0003 -2.212
0.0002 -2.205 0.0002 -2.200
0.0007 -2.192 0.0002 -2.187
0.0005 -2.180 0.0002 -2.176
0.0001 -2.167 0.0002 -2.165
0.0003 -2.156 0.0002 -2.153
0.0003 -2.145 0.0002 -2.143
0.0007 -2.134 0.0002 -2.128
0.0009 -2.121 0.0005 -2.120
0.0007 -2.099 0.0007 -2.099
0.0005 -2.079 0.0004 -2.076
0.0008 -2.039 0.0005 -2.036
0.0012 -2.055 0.0007 -2.058
0.0007 -2.015 0.0009 -2.019
0.0009 -1.994 0.0006 -2.004
0.0010 -1.966 0.0008 -1.983
0.0004 -1.944 0.0013 -1.965
0.0012 -1.920 0.0006 -1.947
0.0003
0.0008
0.0004
0.0005
0.0007
0.0006
0.0006
0.0005
0.0004
0.0008
0.0009
0.0003
0.0004
0.0009
0.0003
0.0006
0.0007
0.0007
0.0006
0.0007
0.0007
0.0006
0.0006
0.0005
0.0008
0.0008
0.0005
0.0006
0.0008
0.0008
0.0005
0.0000
0.0007
0.0009
0.0004
0.0002
0.0002
0.0003
0.0003
0.0003
0.0002
0.0002
0.0003
0.0002
0.0001
0.0002
0.0002
0.0003
0.0004
0.0002
0.0004
0.0004
0.0005
0.0006
0.0002
0.0005
0.0003
0.0003
0.0005
0.0005
0.0002
0.0010
0.0013
0.0015
0.0017
0.0011
0.0011
0.0006
0.0013
0.0016
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
3.00
-2.397
-2.386
-2.377
-2.365
-2.351
-2.335
-2.325
-2.312
-2.301
-2.288
-2.266
-2.254
-2.242
-2.233
-2.223
-2.273
-2.210
-2.196
-2.183
-2.172
-2.160
-2.147
-2.135
-2.123
-2.112
-2.096
-2.078
-2.053
-2.016
-2.032
-1.982
-1.969
-1.953
-1.939
-1.929
-2.396
-2.390
-2.383
-2.370
-2.354
-2.343
-2.329
-2.316
-2.304
-2.291
-2.268
-2.257
-2.245
-2.235
-2.223
-2.281
-2.210
-2.197
-2.184
-2.171
-2.158
-2.148
-2.135
-2.124
-2.113
-2.101
-2.080
-2.056
-2.016
-2.035
-1.990
-1.966
-1.952
-1.930
-1.910
0.0005
0.0003
0.0004
0.0002
0.0005
0.0002
0.0005
0.0003
0.0003
0.0002
0.0003
0.0003
0.0002
0.0001
0.0006
0.0001
0.0004
0.0002
0.0004
0.0007
0.0005
0.0002
0.0003
0.0003
0.0001
0.0003
0.0004
0.0009
0.0003
0.0007
0.0014
0.0011
0.0005
0.0019
0.0013
0.0006
0.0003
0.0008
0.0017
0.0005
0.0005
0.0006
0.0010
0.0012
0.0007
0.0007
0.0019
0.0008
0.0007
0.0005
0.0007
0.0010
0.0007
0.0008
0.0013
0.0008
0.0005
0.0008
0.0004
0.0007
0.0010
0.0012
0.0011
0.0014
0.0010
0.0007
0.0010
0.0006
0.0013
0.0004
S33
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0004
0.0006
0.0008
0.0004
0.0008
0.0008
0.0007
0.0008
0.0005
0.0008
0.0007
0.0011
0.0007
0.0003
0.0002
0.0008
0.0004
0.0005
0.0008
0.0001
0.0001
0.0005
0.0004
0.0007
0.0004
0.0009
0.0007
0.0008
0.0006
0.0011
0.0026
0.0019
0.0009
0.0009
0.0012
-2.393
-2.389
-2.383
-2.366
-2.351
-2.337
-2.328
-2.311
-2.302
-2.287
-2.266
-2.255
-2.245
-2.229
-2.224
-2.276
-2.209
-2.197
-2.184
-2.171
-2.159
-2.145
-2.133
-2.122
-2.113
-2.101
-2.078
-2.053
-2.019
-2.033
-1.997
-1.980
-1.951
-1.934
-1.908
0.0005
0.0007
0.0003
0.0004
0.0003
0.0006
0.0004
0.0006
0.0003
0.0007
0.0009
0.0004
0.0009
0.0006
0.0004
0.0004
0.0004
0.0003
0.0002
0.0004
0.0003
0.0006
0.0005
0.0004
0.0003
0.0003
0.0007
0.0006
0.0005
0.0011
0.0005
0.0008
0.0011
0.0013
0.0011
-2.394
-2.387
-2.377
-2.359
-2.350
-2.339
-2.326
-2.308
-2.294
-2.282
-2.261
-2.243
-2.233
-2.231
-2.217
-2.275
-2.204
-2.192
-2.179
-2.165
-2.155
-2.145
-2.131
-2.121
-2.110
-2.098
-2.077
-2.053
-2.014
-2.036
-1.994
-1.972
-1.961
-1.939
-1.931
Points
R1
R2
2.04 1.64
2.04 1.66
2.04 1.68
2.04 1.72
2.04 1.76
2.04 1.80
2.04 1.84
2.04 1.88
2.04 1.92
2.04 1.96
2.04 2.00
2.04 2.04
2.04 2.08
2.04 2.12
2.04 2.16
2.04 2.20
2.04 2.25
2.04 2.30
2.04 2.35
2.04 2.40
2.04 2.45
2.04 2.50
2.04 2.55
2.04 2.60
2.04 2.65
2.04 2.70
2.04 2.80
2.04 2.90
2.04 3.00
2.04 3.10
2.04 3.20
2.04 3.30
2.04 3.40
2.04 3.50
2.04 3.60
Corrections from
Case A
-2.626 0.0001
-2.619 0.0001
-2.612 0.0002
-2.597 0.0002
-2.584 0.0004
-2.571 0.0002
-2.558 0.0003
-2.545 0.0002
-2.532 0.0003
-2.520 0.0005
-2.495 0.0003
-2.484 0.0004
-2.472 0.0006
-2.463 0.0003
-2.452 0.0001
-2.508 0.0002
-2.440 0.0001
-2.425 0.0003
-2.413 0.0003
-2.401 0.0002
-2.388 0.0003
-2.377 0.0003
-2.363 0.0004
-2.352 0.0003
-2.341 0.0002
-2.330 0.0003
-2.306 0.0004
-2.285 0.0006
-2.245 0.0004
-2.224 0.0006
-2.265 0.0006
-2.206 0.0004
-2.185 0.0007
-2.161 0.0019
-2.139 0.0010
Fixman
Case B
-2.626
-2.619
-2.612
-2.599
-2.585
-2.570
-2.559
-2.546
-2.533
-2.521
-2.498
-2.486
-2.475
-2.463
-2.453
-2.509
-2.440
-2.426
-2.412
-2.400
-2.388
-2.376
-2.363
-2.352
-2.340
-2.329
-2.307
-2.286
-2.245
-2.223
-2.265
-2.204
-2.187
-2.168
-2.150
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0005 -2.626 0.0001 -2.625
0.0003 -2.619 0.0002 -2.619
0.0004 -2.611 0.0004 -2.611
0.0001 -2.598 0.0003 -2.597
0.0001 -2.584 0.0003 -2.583
0.0003 -2.571 0.0002 -2.570
0.0001 -2.558 0.0002 -2.557
0.0001 -2.545 0.0003 -2.544
0.0003 -2.532 0.0004 -2.532
0.0003 -2.519 0.0004 -2.519
0.0003 -2.496 0.0005 -2.495
0.0001 -2.484 0.0002 -2.484
0.0000 -2.472 0.0003 -2.473
0.0005 -2.461 0.0003 -2.461
0.0001 -2.453 0.0001 -2.450
0.0002 -2.506 0.0004 -2.508
0.0001 -2.440 0.0001 -2.437
0.0002 -2.426 0.0002 -2.424
0.0002 -2.413 0.0002 -2.411
0.0004 -2.401 0.0002 -2.398
0.0002 -2.389 0.0002 -2.385
0.0004 -2.375 0.0005 -2.376
0.0008 -2.365 0.0002 -2.362
0.0003 -2.353 0.0003 -2.352
0.0006 -2.336 0.0008 -2.340
0.0005 -2.330 0.0005 -2.330
0.0003 -2.306 0.0007 -2.305
0.0004 -2.281 0.0008 -2.285
0.0004 -2.246 0.0002 -2.245
0.0008 -2.222 0.0008 -2.209
0.0008 -2.261 0.0006 -2.267
0.0008 -2.204 0.0006 -2.194
0.0008 -2.178 0.0016 -2.161
0.0006 -2.157 0.0008 -2.154
0.0009 -2.141 0.0021 -2.125
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
2.08
-2.615
-2.608
-2.600
-2.586
-2.573
-2.559
-2.546
-2.533
-2.521
-2.508
-2.484
-2.472
-2.461
-2.449
-2.441
-2.496
-2.428
-2.415
-2.402
-2.389
-2.377
-2.364
-2.352
-2.339
-2.329
-2.317
-2.294
-2.273
-2.232
-2.212
-2.252
-2.192
-2.171
-2.150
-2.134
-2.614
-2.607
-2.600
-2.585
-2.574
-2.559
-2.545
-2.535
-2.522
-2.510
-2.486
-2.474
-2.463
-2.451
-2.441
-2.498
-2.427
-2.414
-2.400
-2.389
-2.377
-2.363
-2.351
-2.340
-2.329
-2.319
-2.295
-2.272
-2.231
-2.213
-2.254
-2.194
-2.176
-2.158
-2.131
0.0002
0.0002
0.0003
0.0005
0.0001
0.0003
0.0003
0.0001
0.0002
0.0002
0.0003
0.0002
0.0001
0.0003
0.0002
0.0002
0.0003
0.0003
0.0007
0.0003
0.0003
0.0008
0.0006
0.0007
0.0004
0.0005
0.0006
0.0006
0.0007
0.0008
0.0005
0.0011
0.0007
0.0005
0.0019
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0003
0.0002
0.0002
0.0002
0.0002
0.0004
0.0002
0.0002
0.0004
0.0003
0.0003
0.0005
0.0002
0.0003
0.0001
0.0004
0.0000
0.0002
0.0002
0.0003
0.0003
0.0004
0.0005
0.0010
0.0003
0.0005
0.0008
0.0006
0.0005
0.0008
0.0007
0.0006
0.0008
0.0019
0.0012
-2.614
-2.607
-2.600
-2.586
-2.572
-2.559
-2.547
-2.533
-2.521
-2.508
-2.485
-2.472
-2.461
-2.449
-2.441
-2.496
-2.428
-2.415
-2.402
-2.389
-2.377
-2.364
-2.352
-2.341
-2.329
-2.316
-2.295
-2.273
-2.234
-2.212
-2.244
-2.190
-2.170
-2.152
-2.121
0.0002
0.0003
0.0003
0.0004
0.0003
0.0003
0.0002
0.0004
0.0002
0.0003
0.0002
0.0003
0.0003
0.0004
0.0001
0.0003
0.0000
0.0002
0.0002
0.0002
0.0003
0.0005
0.0004
0.0007
0.0002
0.0006
0.0008
0.0007
0.0005
0.0007
0.0024
0.0010
0.0010
0.0017
0.0020
-2.614
-2.607
-2.599
-2.585
-2.571
-2.559
-2.546
-2.533
-2.521
-2.507
-2.483
-2.473
-2.462
-2.450
-2.439
-2.494
-2.426
-2.413
-2.397
-2.388
-2.375
-2.363
-2.352
-2.342
-2.330
-2.318
-2.296
-2.277
-2.235
-2.216
-2.253
-2.199
-2.177
-2.157
-2.147
0.0002
0.0002
0.0003
0.0003
0.0002
0.0003
0.0005
0.0002
0.0004
0.0003
0.0004
0.0005
0.0003
0.0004
0.0004
0.0003
0.0005
0.0003
0.0004
0.0004
0.0004
0.0003
0.0006
0.0003
0.0008
0.0003
0.0013
0.0004
0.0009
0.0017
0.0005
0.0013
0.0007
0.0024
0.0002
Points
R1
R2
3.10 1.64
3.10 1.66
3.10 1.68
3.10 1.72
3.10 1.76
3.10 1.80
3.10 1.84
3.10 1.88
3.10 1.92
3.10 1.96
3.10 2.00
3.10 2.04
3.10 2.08
3.10 2.12
3.10 2.16
3.10 2.20
3.10 2.25
3.10 2.30
3.10 2.35
3.10 2.40
3.10 2.45
3.10 2.50
3.10 2.55
3.10 2.60
3.10 2.65
3.10 2.70
3.10 2.80
3.10 2.90
3.10 3.00
3.10 3.10
3.10 3.20
3.10 3.30
3.10 3.40
3.10 3.50
3.10 3.60
Corrections from
Case A
-2.372 0.0006
-2.365 0.0004
-2.357 0.0007
-2.347 0.0009
-2.327 0.0018
-2.312 0.0009
-2.300 0.0017
-2.289 0.0009
-2.279 0.0007
-2.268 0.0007
-2.246 0.0003
-2.230 0.0010
-2.220 0.0006
-2.206 0.0007
-2.204 0.0003
-2.251 0.0010
-2.187 0.0008
-2.176 0.0006
-2.164 0.0006
-2.152 0.0003
-2.139 0.0005
-2.126 0.0006
-2.116 0.0003
-2.103 0.0006
-2.093 0.0005
-2.076 0.0017
-2.057 0.0006
-2.038 0.0006
-1.995 0.0012
-2.012 0.0012
-1.975 0.0019
-1.963 0.0007
-1.935 0.0012
-1.916 0.0011
-1.907 0.0009
Fixman
Case B
-2.379
-2.371
-2.364
-2.348
-2.336
-2.323
-2.310
-2.297
-2.284
-2.273
-2.248
-2.235
-2.225
-2.212
-2.203
-2.261
-2.191
-2.178
-2.164
-2.150
-2.138
-2.128
-2.115
-2.105
-2.093
-2.080
-2.055
-2.032
-1.998
-2.014
-1.971
-1.959
-1.930
-1.909
-1.898
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0001 -2.375 0.0006 -2.371
0.0003 -2.362 0.0015 -2.367
0.0002 -2.363 0.0005 -2.359
0.0004 -2.346 0.0007 -2.341
0.0003 -2.335 0.0011 -2.324
0.0002 -2.316 0.0012 -2.318
0.0003 -2.303 0.0007 -2.301
0.0003 -2.292 0.0013 -2.286
0.0003 -2.277 0.0012 -2.278
0.0003 -2.265 0.0010 -2.264
0.0005 -2.243 0.0005 -2.242
0.0008 -2.228 0.0004 -2.228
0.0003 -2.225 0.0005 -2.218
0.0008 -2.215 0.0004 -2.206
0.0004 -2.204 0.0003 -2.197
0.0002 -2.253 0.0010 -2.246
0.0003 -2.190 0.0004 -2.184
0.0003 -2.176 0.0009 -2.169
0.0002 -2.166 0.0000 -2.148
0.0007 -2.152 0.0005 -2.141
0.0003 -2.139 0.0003 -2.132
0.0003 -2.125 0.0010 -2.121
0.0003 -2.115 0.0007 -2.109
0.0003 -2.105 0.0002 -2.092
0.0005 -2.093 0.0006 -2.082
0.0007 -2.082 0.0003 -2.076
0.0013 -2.058 0.0006 -2.051
0.0016 -2.034 0.0012 -2.035
0.0003 -1.995 0.0009 -1.997
0.0011 -2.019 0.0004 -2.014
0.0013 -1.971 0.0010 -1.982
0.0014 -1.950 0.0008 -1.961
0.0012 -1.927 0.0006 -1.945
0.0022 -1.913 0.0019 -1.926
0.0005 -1.882 0.0011 -1.903
0.0005
0.0008
0.0007
0.0016
0.0015
0.0005
0.0010
0.0020
0.0008
0.0009
0.0005
0.0015
0.0006
0.0012
0.0007
0.0025
0.0005
0.0006
0.0025
0.0008
0.0012
0.0004
0.0007
0.0005
0.0007
0.0009
0.0013
0.0006
0.0014
0.0008
0.0003
0.0008
0.0004
0.0006
0.0009
0.0003
0.0003
0.0004
0.0003
0.0003
0.0002
0.0003
0.0003
0.0002
0.0004
0.0004
0.0004
0.0003
0.0003
0.0005
0.0005
0.0002
0.0006
0.0006
0.0005
0.0004
0.0003
0.0005
0.0002
0.0006
0.0004
0.0004
0.0001
0.0003
0.0005
0.0005
0.0003
0.0014
0.0019
0.0006
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
3.20
-2.352
-2.346
-2.337
-2.322
-2.311
-2.283
-2.284
-2.268
-2.255
-2.243
-2.219
-2.202
-2.206
-2.196
-2.184
-2.234
-2.172
-2.157
-2.146
-2.133
-2.118
-2.107
-2.097
-2.085
-2.065
-2.062
-2.037
-2.013
-1.977
-2.001
-1.957
-1.930
-1.923
-1.891
-1.881
-2.360
-2.353
-2.345
-2.331
-2.318
-2.304
-2.290
-2.279
-2.265
-2.253
-2.230
-2.217
-2.206
-2.196
-2.185
-2.242
-2.168
-2.156
-2.146
-2.133
-2.118
-2.107
-2.095
-2.084
-2.074
-2.058
-2.038
-2.014
-1.958
-1.989
-1.954
-1.933
-1.893
-1.893
-1.861
0.0002
0.0001
0.0002
0.0002
0.0003
0.0002
0.0005
0.0002
0.0004
0.0005
0.0002
0.0004
0.0005
0.0004
0.0002
0.0001
0.0016
0.0006
0.0005
0.0006
0.0012
0.0004
0.0009
0.0006
0.0005
0.0014
0.0011
0.0007
0.0029
0.0013
0.0009
0.0018
0.0002
0.0007
0.0007
0.0008
0.0016
0.0016
0.0010
0.0005
0.0009
0.0011
0.0016
0.0017
0.0021
0.0007
0.0008
0.0023
0.0006
0.0029
0.0010
0.0007
0.0016
0.0012
0.0007
0.0008
0.0016
0.0019
0.0013
0.0012
0.0009
0.0008
0.0013
0.0006
0.0010
0.0009
0.0009
0.0006
0.0007
0.0006
S34
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0004
0.0005
0.0004
0.0016
0.0008
0.0023
0.0007
0.0024
0.0010
0.0013
0.0017
0.0017
0.0004
0.0003
0.0003
0.0010
0.0004
0.0009
0.0004
0.0003
0.0006
0.0007
0.0003
0.0004
0.0009
0.0007
0.0010
0.0019
0.0009
0.0002
0.0012
0.0014
0.0013
0.0020
0.0006
-2.347
-2.342
-2.338
-2.322
-2.317
-2.283
-2.285
-2.264
-2.257
-2.242
-2.225
-2.213
-2.206
-2.196
-2.182
-2.229
-2.172
-2.157
-2.146
-2.133
-2.121
-2.107
-2.097
-2.084
-2.075
-2.064
-2.039
-2.021
-1.980
-2.001
-1.959
-1.940
-1.917
-1.888
-1.867
0.0013
0.0010
0.0015
0.0010
0.0003
0.0016
0.0007
0.0011
0.0007
0.0009
0.0011
0.0008
0.0006
0.0005
0.0006
0.0008
0.0001
0.0004
0.0003
0.0005
0.0002
0.0006
0.0003
0.0006
0.0003
0.0002
0.0006
0.0003
0.0005
0.0005
0.0004
0.0009
0.0008
0.0010
0.0023
-2.333
-2.331
-2.335
-2.321
-2.311
-2.294
-2.258
-2.267
-2.243
-2.240
-2.224
-2.212
-2.194
-2.189
-2.162
-2.230
-2.164
-2.146
-2.136
-2.127
-2.114
-2.099
-2.089
-2.079
-2.066
-2.056
-2.034
-2.010
-1.979
-1.993
-1.954
-1.936
-1.917
-1.899
-1.876
Points
R1
R2
2.12 1.64
2.12 1.66
2.12 1.68
2.12 1.72
2.12 1.76
2.12 1.80
2.12 1.84
2.12 1.88
2.12 1.92
2.12 1.96
2.12 2.00
2.12 2.04
2.12 2.08
2.12 2.12
2.12 2.16
2.12 2.20
2.12 2.25
2.12 2.30
2.12 2.35
2.12 2.40
2.12 2.45
2.12 2.50
2.12 2.55
2.12 2.60
2.12 2.65
2.12 2.70
2.12 2.80
2.12 2.90
2.12 3.00
2.12 3.10
2.12 3.20
2.12 3.30
2.12 3.40
2.12 3.50
2.12 3.60
Corrections from
Case A
-2.603 0.0002
-2.596 0.0002
-2.589 0.0002
-2.575 0.0002
-2.561 0.0003
-2.547 0.0004
-2.535 0.0003
-2.522 0.0002
-2.509 0.0003
-2.497 0.0003
-2.473 0.0003
-2.460 0.0003
-2.450 0.0002
-2.438 0.0004
-2.430 0.0002
-2.484 0.0002
-2.417 0.0001
-2.404 0.0001
-2.391 0.0001
-2.378 0.0003
-2.366 0.0002
-2.353 0.0002
-2.340 0.0008
-2.329 0.0005
-2.315 0.0010
-2.304 0.0004
-2.283 0.0007
-2.261 0.0011
-2.216 0.0012
-2.198 0.0007
-2.241 0.0007
-2.182 0.0006
-2.163 0.0008
-2.142 0.0018
-2.117 0.0010
Fixman
Case B
-2.603
-2.596
-2.588
-2.575
-2.561
-2.549
-2.534
-2.520
-2.511
-2.498
-2.474
-2.463
-2.451
-2.440
-2.429
-2.487
-2.416
-2.403
-2.390
-2.378
-2.364
-2.353
-2.340
-2.327
-2.316
-2.307
-2.284
-2.262
-2.221
-2.201
-2.241
-2.182
-2.164
-2.132
-2.126
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0002 -2.603 0.0002 -2.602
0.0003 -2.596 0.0003 -2.595
0.0003 -2.589 0.0003 -2.589
0.0003 -2.575 0.0003 -2.574
0.0002 -2.561 0.0003 -2.560
0.0004 -2.548 0.0003 -2.547
0.0002 -2.534 0.0004 -2.534
0.0005 -2.522 0.0004 -2.521
0.0001 -2.509 0.0002 -2.508
0.0002 -2.496 0.0004 -2.498
0.0002 -2.473 0.0003 -2.472
0.0003 -2.461 0.0003 -2.461
0.0005 -2.450 0.0003 -2.450
0.0002 -2.439 0.0004 -2.438
0.0002 -2.430 0.0002 -2.427
0.0001 -2.485 0.0003 -2.484
0.0006 -2.417 0.0000 -2.415
0.0004 -2.403 0.0002 -2.402
0.0004 -2.391 0.0001 -2.388
0.0004 -2.378 0.0002 -2.375
0.0008 -2.365 0.0003 -2.363
0.0003 -2.353 0.0003 -2.352
0.0004 -2.341 0.0003 -2.340
0.0007 -2.331 0.0002 -2.328
0.0008 -2.317 0.0003 -2.318
0.0007 -2.305 0.0011 -2.306
0.0005 -2.280 0.0020 -2.286
0.0008 -2.261 0.0010 -2.257
0.0006 -2.209 0.0020 -2.224
0.0007 -2.201 0.0006 -2.205
0.0006 -2.241 0.0011 -2.245
0.0011 -2.182 0.0008 -2.168
0.0010 -2.156 0.0009 -2.169
0.0024 -2.142 0.0012 -2.150
0.0009 -2.123 0.0004 -2.133
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
2.16
-2.592
-2.586
-2.578
-2.564
-2.550
-2.537
-2.523
-2.511
-2.498
-2.486
-2.461
-2.450
-2.439
-2.429
-2.419
-2.473
-2.406
-2.392
-2.378
-2.367
-2.354
-2.343
-2.330
-2.318
-2.305
-2.296
-2.271
-2.251
-2.206
-2.179
-2.232
-2.169
-2.149
-2.127
-2.112
-2.593
-2.585
-2.576
-2.564
-2.551
-2.536
-2.525
-2.512
-2.499
-2.486
-2.464
-2.452
-2.441
-2.429
-2.418
-2.475
-2.405
-2.392
-2.379
-2.366
-2.354
-2.342
-2.329
-2.318
-2.306
-2.293
-2.272
-2.251
-2.208
-2.190
-2.230
-2.161
-2.151
-2.110
-2.120
0.0001
0.0004
0.0005
0.0003
0.0003
0.0005
0.0003
0.0002
0.0002
0.0004
0.0002
0.0002
0.0002
0.0002
0.0003
0.0002
0.0004
0.0002
0.0004
0.0004
0.0004
0.0005
0.0004
0.0005
0.0007
0.0007
0.0009
0.0008
0.0008
0.0007
0.0005
0.0012
0.0009
0.0011
0.0005
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0002
0.0002
0.0003
0.0003
0.0002
0.0004
0.0002
0.0003
0.0002
0.0006
0.0004
0.0004
0.0002
0.0001
0.0003
0.0001
0.0003
0.0004
0.0001
0.0003
0.0001
0.0003
0.0007
0.0009
0.0005
0.0007
0.0006
0.0007
0.0029
0.0005
0.0011
0.0016
0.0025
0.0017
-2.592
-2.584
-2.577
-2.564
-2.550
-2.537
-2.523
-2.511
-2.498
-2.486
-2.461
-2.450
-2.438
-2.429
-2.419
-2.474
-2.405
-2.391
-2.378
-2.367
-2.354
-2.341
-2.330
-2.319
-2.304
-2.291
-2.272
-2.244
-2.208
-2.184
-2.228
-2.169
-2.135
-2.135
-2.109
0.0002
0.0003
0.0003
0.0003
0.0002
0.0001
0.0004
0.0003
0.0002
0.0002
0.0003
0.0005
0.0002
0.0003
0.0001
0.0003
0.0003
0.0006
0.0004
0.0001
0.0002
0.0005
0.0005
0.0004
0.0006
0.0018
0.0007
0.0015
0.0011
0.0008
0.0007
0.0012
0.0028
0.0019
0.0016
-2.591
-2.584
-2.576
-2.563
-2.549
-2.536
-2.522
-2.509
-2.497
-2.485
-2.461
-2.449
-2.436
-2.429
-2.416
-2.473
-2.402
-2.390
-2.377
-2.364
-2.352
-2.340
-2.325
-2.316
-2.305
-2.292
-2.272
-2.253
-2.214
-2.195
-2.232
-2.175
-2.159
-2.141
-2.126
0.0002
0.0003
0.0002
0.0002
0.0001
0.0003
0.0003
0.0004
0.0005
0.0003
0.0004
0.0003
0.0002
0.0003
0.0004
0.0003
0.0004
0.0004
0.0004
0.0004
0.0006
0.0006
0.0005
0.0007
0.0005
0.0004
0.0004
0.0019
0.0006
0.0008
0.0004
0.0026
0.0003
0.0006
0.0005
Points
R1
R2
3.30 1.64
3.30 1.66
3.30 1.68
3.30 1.72
3.30 1.76
3.30 1.80
3.30 1.84
3.30 1.88
3.30 1.92
3.30 1.96
3.30 2.00
3.30 2.04
3.30 2.08
3.30 2.12
3.30 2.16
3.30 2.20
3.30 2.25
3.30 2.30
3.30 2.35
3.30 2.40
3.30 2.45
3.30 2.50
3.30 2.55
3.30 2.60
3.30 2.65
3.30 2.70
3.30 2.80
3.30 2.90
3.30 3.00
3.30 3.10
3.30 3.20
3.30 3.30
3.30 3.40
3.30 3.50
3.30 3.60
Corrections from
Case A
-2.327 0.0017
-2.323 0.0007
-2.320 0.0007
-2.304 0.0005
-2.274 0.0017
-2.277 0.0009
-2.263 0.0015
-2.244 0.0014
-2.242 0.0006
-2.226 0.0006
-2.209 0.0006
-2.189 0.0016
-2.185 0.0004
-2.169 0.0013
-2.205 0.0023
-2.163 0.0018
-2.153 0.0003
-2.139 0.0005
-2.127 0.0008
-2.116 0.0002
-2.103 0.0002
-2.090 0.0005
-2.077 0.0007
-2.067 0.0008
-2.052 0.0007
-2.041 0.0007
-2.020 0.0007
-2.001 0.0003
-1.959 0.0013
-1.980 0.0007
-1.937 0.0006
-1.906 0.0009
-1.903 0.0002
-1.884 0.0013
-1.872 0.0006
Fixman
Case B
-2.341
-2.334
-2.327
-2.312
-2.299
-2.286
-2.272
-2.259
-2.246
-2.235
-2.212
-2.200
-2.189
-2.176
-2.166
-2.224
-2.153
-2.140
-2.128
-2.114
-2.100
-2.091
-2.079
-2.066
-2.054
-2.045
-2.023
-2.001
-1.946
-1.973
-1.935
-1.892
-1.897
-1.877
-1.858
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0003 -2.340 0.0005 -2.316
0.0003 -2.322 0.0012 -2.326
0.0002 -2.327 0.0003 -2.310
0.0004 -2.305 0.0013 -2.299
0.0005 -2.291 0.0017 -2.284
0.0003 -2.279 0.0009 -2.275
0.0004 -2.263 0.0010 -2.261
0.0005 -2.252 0.0009 -2.245
0.0005 -2.234 0.0007 -2.219
0.0004 -2.222 0.0013 -2.209
0.0003 -2.212 0.0003 -2.178
0.0004 -2.190 0.0012 -2.182
0.0003 -2.180 0.0018 -2.172
0.0006 -2.178 0.0004 -2.147
0.0006 -2.211 0.0011 -2.147
0.0001 -2.167 0.0002 -2.219
0.0003 -2.152 0.0006 -2.121
0.0005 -2.141 0.0003 -2.131
0.0003 -2.127 0.0006 -2.113
0.0009 -2.115 0.0004 -2.102
0.0008 -2.102 0.0005 -2.091
0.0002 -2.090 0.0010 -2.080
0.0003 -2.079 0.0003 -2.068
0.0006 -2.066 0.0004 -2.062
0.0011 -2.055 0.0004 -2.045
0.0003 -2.043 0.0006 -2.036
0.0005 -2.019 0.0019 -2.015
0.0004 -2.003 0.0003 -1.996
0.0015 -1.961 0.0007 -1.963
0.0012 -1.981 0.0005 -1.976
0.0011 -1.936 0.0010 -1.938
0.0004 -1.920 0.0006 -1.925
0.0010 -1.897 0.0011 -1.904
0.0020 -1.869 0.0006 -1.886
0.0012 -1.862 0.0015 -1.865
0.0010
0.0008
0.0027
0.0013
0.0012
0.0015
0.0012
0.0009
0.0012
0.0022
0.0004
0.0014
0.0006
0.0012
0.0022
0.0009
0.0009
0.0013
0.0007
0.0009
0.0010
0.0012
0.0006
0.0010
0.0008
0.0011
0.0005
0.0009
0.0004
0.0007
0.0007
0.0005
0.0010
0.0004
0.0011
0.0003
0.0003
0.0004
0.0002
0.0002
0.0003
0.0002
0.0003
0.0003
0.0005
0.0003
0.0004
0.0007
0.0002
0.0005
0.0003
0.0005
0.0003
0.0005
0.0006
0.0004
0.0006
0.0007
0.0005
0.0009
0.0007
0.0006
0.0004
0.0004
0.0002
0.0006
0.0009
0.0004
0.0008
0.0004
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
3.40
-2.305
-2.300
-2.294
-2.288
-2.268
-2.260
-2.240
-2.228
-2.217
-2.205
-2.193
-2.163
-2.168
-2.147
-2.198
-2.149
-2.135
-2.123
-2.110
-2.097
-2.084
-2.070
-2.061
-2.049
-2.035
-2.026
-2.005
-1.985
-1.940
-1.963
-1.923
-1.895
-1.887
-1.866
-1.832
-2.322
-2.316
-2.309
-2.294
-2.281
-2.268
-2.255
-2.242
-2.230
-2.218
-2.194
-2.183
-2.169
-2.158
-2.205
-2.148
-2.135
-2.121
-2.110
-2.097
-2.085
-2.073
-2.060
-2.049
-2.034
-2.025
-2.004
-1.974
-1.938
-1.954
-1.917
-1.896
-1.876
-1.844
-1.836
0.0003
0.0003
0.0002
0.0004
0.0004
0.0004
0.0004
0.0003
0.0002
0.0001
0.0002
0.0003
0.0005
0.0005
0.0005
0.0005
0.0005
0.0006
0.0003
0.0006
0.0005
0.0005
0.0005
0.0004
0.0016
0.0005
0.0004
0.0015
0.0016
0.0005
0.0013
0.0027
0.0018
0.0007
0.0013
0.0009
0.0007
0.0013
0.0011
0.0009
0.0006
0.0008
0.0015
0.0006
0.0009
0.0011
0.0013
0.0007
0.0009
0.0013
0.0009
0.0007
0.0011
0.0006
0.0009
0.0009
0.0019
0.0012
0.0039
0.0006
0.0016
0.0005
0.0006
0.0014
0.0013
0.0019
0.0011
0.0009
0.0015
0.0007
S35
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0011
0.0011
0.0009
0.0013
0.0013
0.0004
0.0016
0.0009
0.0008
0.0014
0.0013
0.0031
0.0006
0.0008
0.0008
0.0005
0.0003
0.0005
0.0004
0.0004
0.0006
0.0008
0.0004
0.0004
0.0013
0.0005
0.0006
0.0003
0.0003
0.0006
0.0010
0.0011
0.0014
0.0009
0.0017
-2.323
-2.302
-2.300
-2.281
-2.274
-2.256
-2.243
-2.232
-2.219
-2.207
-2.192
-2.170
-2.171
-2.159
-2.194
-2.149
-2.135
-2.122
-2.108
-2.097
-2.084
-2.072
-2.061
-2.047
-2.035
-2.024
-2.004
-1.975
-1.937
-1.961
-1.924
-1.907
-1.868
-1.861
-1.843
0.0004
0.0011
0.0006
0.0025
0.0023
0.0008
0.0011
0.0006
0.0010
0.0005
0.0004
0.0015
0.0003
0.0005
0.0008
0.0002
0.0004
0.0004
0.0008
0.0004
0.0007
0.0007
0.0003
0.0010
0.0005
0.0016
0.0008
0.0024
0.0008
0.0011
0.0008
0.0005
0.0011
0.0010
0.0020
-2.315
-2.303
-2.294
-2.284
-2.272
-2.256
-2.245
-2.211
-2.220
-2.206
-2.181
-2.169
-2.155
-2.149
-2.189
-2.137
-2.127
-2.109
-2.100
-2.089
-2.074
-2.051
-2.051
-2.038
-2.029
-2.013
-1.991
-1.972
-1.932
-1.946
-1.913
-1.888
-1.859
-1.860
-1.855
Points
R1
R2
2.20 1.64
2.20 1.66
2.20 1.68
2.20 1.72
2.20 1.76
2.20 1.80
2.20 1.84
2.20 1.88
2.20 1.92
2.20 1.96
2.20 2.00
2.20 2.04
2.20 2.08
2.20 2.12
2.20 2.16
2.20 2.20
2.20 2.25
2.20 2.30
2.20 2.35
2.20 2.40
2.20 2.45
2.20 2.50
2.20 2.55
2.20 2.60
2.20 2.65
2.20 2.70
2.20 2.80
2.20 2.90
2.20 3.00
2.20 3.10
2.20 3.20
2.20 3.30
2.20 3.40
2.20 3.50
2.20 3.60
Corrections from
Case A
-2.582 0.0002
-2.574 0.0002
-2.566 0.0002
-2.551 0.0004
-2.539 0.0005
-2.525 0.0004
-2.513 0.0002
-2.499 0.0003
-2.487 0.0003
-2.475 0.0004
-2.451 0.0003
-2.439 0.0004
-2.428 0.0004
-2.417 0.0003
-2.407 0.0003
-2.462 0.0004
-2.394 0.0003
-2.381 0.0003
-2.368 0.0003
-2.356 0.0002
-2.343 0.0004
-2.332 0.0003
-2.319 0.0005
-2.306 0.0009
-2.294 0.0004
-2.283 0.0008
-2.255 0.0013
-2.239 0.0006
-2.199 0.0008
-2.179 0.0006
-2.220 0.0009
-2.159 0.0013
-2.141 0.0009
-2.121 0.0006
-2.096 0.0010
Fixman
Case B
-2.580
-2.574
-2.567
-2.553
-2.540
-2.527
-2.514
-2.501
-2.488
-2.476
-2.453
-2.441
-2.430
-2.419
-2.407
-2.465
-2.394
-2.381
-2.367
-2.355
-2.343
-2.330
-2.319
-2.307
-2.296
-2.281
-2.260
-2.231
-2.195
-2.178
-2.218
-2.158
-2.142
-2.116
-2.104
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0005 -2.581 0.0003 -2.580
0.0003 -2.574 0.0004 -2.573
0.0002 -2.566 0.0003 -2.565
0.0004 -2.553 0.0001 -2.553
0.0001 -2.539 0.0003 -2.538
0.0003 -2.526 0.0003 -2.525
0.0003 -2.512 0.0003 -2.511
0.0001 -2.499 0.0004 -2.498
0.0003 -2.487 0.0003 -2.486
0.0001 -2.475 0.0004 -2.473
0.0002 -2.450 0.0007 -2.449
0.0002 -2.440 0.0003 -2.439
0.0002 -2.427 0.0006 -2.426
0.0001 -2.416 0.0006 -2.418
0.0005 -2.408 0.0001 -2.407
0.0001 -2.463 0.0003 -2.461
0.0006 -2.395 0.0001 -2.391
0.0003 -2.381 0.0003 -2.379
0.0005 -2.368 0.0004 -2.368
0.0004 -2.356 0.0002 -2.354
0.0002 -2.343 0.0003 -2.343
0.0008 -2.330 0.0003 -2.329
0.0007 -2.320 0.0002 -2.320
0.0005 -2.307 0.0005 -2.305
0.0004 -2.293 0.0009 -2.293
0.0013 -2.283 0.0008 -2.286
0.0006 -2.260 0.0013 -2.261
0.0021 -2.239 0.0005 -2.242
0.0015 -2.196 0.0007 -2.201
0.0005 -2.214 0.0019 -2.182
0.0002 -2.180 0.0010 -2.223
0.0010 -2.158 0.0014 -2.152
0.0010 -2.137 0.0014 -2.146
0.0018 -2.122 0.0008 -2.123
0.0014 -2.100 0.0010 -2.101
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
2.25
-2.568
-2.561
-2.553
-2.539
-2.525
-2.513
-2.499
-2.486
-2.474
-2.462
-2.437
-2.426
-2.415
-2.404
-2.395
-2.449
-2.380
-2.368
-2.355
-2.343
-2.329
-2.318
-2.305
-2.294
-2.280
-2.271
-2.243
-2.226
-2.178
-2.204
-2.161
-2.147
-2.127
-2.102
-2.088
-2.568
-2.562
-2.555
-2.541
-2.527
-2.514
-2.501
-2.488
-2.476
-2.463
-2.440
-2.428
-2.417
-2.406
-2.395
-2.452
-2.381
-2.367
-2.354
-2.343
-2.329
-2.317
-2.306
-2.292
-2.281
-2.271
-2.249
-2.227
-2.185
-2.204
-2.164
-2.145
-2.128
-2.107
-2.091
0.0004
0.0002
0.0001
0.0001
0.0001
0.0001
0.0001
0.0001
0.0000
0.0001
0.0001
0.0002
0.0001
0.0001
0.0002
0.0001
0.0002
0.0006
0.0004
0.0003
0.0005
0.0004
0.0004
0.0003
0.0005
0.0005
0.0005
0.0007
0.0010
0.0021
0.0006
0.0005
0.0017
0.0029
0.0009
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0003
0.0002
0.0003
0.0003
0.0004
0.0003
0.0004
0.0002
0.0003
0.0003
0.0007
0.0003
0.0003
0.0006
0.0001
0.0003
0.0003
0.0002
0.0003
0.0003
0.0002
0.0003
0.0005
0.0006
0.0010
0.0005
0.0017
0.0007
0.0015
0.0008
0.0020
0.0010
0.0006
0.0021
0.0019
-2.567
-2.561
-2.553
-2.540
-2.525
-2.512
-2.499
-2.487
-2.473
-2.461
-2.438
-2.426
-2.414
-2.402
-2.395
-2.449
-2.381
-2.368
-2.355
-2.342
-2.331
-2.318
-2.305
-2.294
-2.280
-2.271
-2.249
-2.224
-2.182
-2.197
-2.162
-2.139
-2.115
-2.101
-2.090
0.0004
0.0002
0.0005
0.0002
0.0004
0.0002
0.0003
0.0002
0.0004
0.0004
0.0003
0.0004
0.0005
0.0003
0.0001
0.0002
0.0001
0.0003
0.0002
0.0003
0.0002
0.0005
0.0006
0.0004
0.0008
0.0004
0.0008
0.0011
0.0003
0.0007
0.0014
0.0008
0.0004
0.0018
0.0011
-2.569
-2.560
-2.553
-2.538
-2.526
-2.512
-2.499
-2.485
-2.473
-2.462
-2.438
-2.426
-2.415
-2.402
-2.391
-2.448
-2.378
-2.366
-2.354
-2.343
-2.329
-2.317
-2.307
-2.295
-2.284
-2.272
-2.251
-2.228
-2.191
-2.208
-2.171
-2.151
-2.131
-2.117
-2.100
0.0004
0.0004
0.0003
0.0002
0.0003
0.0002
0.0004
0.0004
0.0003
0.0005
0.0004
0.0004
0.0005
0.0003
0.0003
0.0004
0.0004
0.0008
0.0003
0.0006
0.0003
0.0005
0.0002
0.0008
0.0004
0.0004
0.0008
0.0005
0.0005
0.0006
0.0006
0.0008
0.0010
0.0025
0.0016
Points
R1
R2
3.50 1.64
3.50 1.66
3.50 1.68
3.50 1.72
3.50 1.76
3.50 1.80
3.50 1.84
3.50 1.88
3.50 1.92
3.50 1.96
3.50 2.00
3.50 2.04
3.50 2.08
3.50 2.12
3.50 2.16
3.50 2.20
3.50 2.25
3.50 2.30
3.50 2.35
3.50 2.40
3.50 2.45
3.50 2.50
3.50 2.55
3.50 2.60
3.50 2.65
3.50 2.70
3.50 2.80
3.50 2.90
3.50 3.00
3.50 3.10
3.50 3.20
3.50 3.30
3.50 3.40
3.50 3.50
3.50 3.60
Corrections from
Case A
-2.294 0.0011
-2.288 0.0009
-2.268 0.0012
-2.268 0.0009
-2.248 0.0013
-2.238 0.0011
-2.225 0.0008
-2.201 0.0012
-2.203 0.0009
-2.190 0.0013
-2.158 0.0021
-2.137 0.0010
-2.153 0.0003
-2.125 0.0020
-2.171 0.0011
-2.132 0.0002
-2.119 0.0002
-2.105 0.0003
-2.090 0.0011
-2.080 0.0004
-2.068 0.0002
-2.057 0.0002
-2.045 0.0002
-2.033 0.0002
-2.017 0.0011
-2.009 0.0008
-1.986 0.0007
-1.964 0.0017
-1.927 0.0005
-1.940 0.0019
-1.904 0.0012
-1.874 0.0013
-1.863 0.0018
-1.854 0.0007
-1.825 0.0009
Fixman
Case B
-2.307
-2.299
-2.293
-2.279
-2.263
-2.252
-2.238
-2.226
-2.212
-2.200
-2.177
-2.166
-2.155
-2.142
-2.189
-2.128
-2.118
-2.104
-2.091
-2.079
-2.068
-2.056
-2.044
-2.033
-2.021
-2.011
-1.989
-1.964
-1.927
-1.938
-1.901
-1.873
-1.854
-1.826
-1.823
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0002 -2.305 0.0004 -2.293
0.0001 -2.284 0.0012 -2.284
0.0001 -2.278 0.0008 -2.280
0.0001 -2.263 0.0012 -2.267
0.0004 -2.245 0.0014 -2.253
0.0001 -2.237 0.0008 -2.240
0.0002 -2.226 0.0010 -2.221
0.0002 -2.212 0.0012 -2.202
0.0004 -2.198 0.0008 -2.199
0.0006 -2.186 0.0007 -2.186
0.0002 -2.176 0.0003 -2.162
0.0000 -2.152 0.0005 -2.152
0.0002 -2.154 0.0003 -2.143
0.0003 -2.139 0.0009 -2.126
0.0002 -2.171 0.0005 -2.181
0.0009 -2.132 0.0002 -2.117
0.0002 -2.119 0.0002 -2.093
0.0007 -2.106 0.0003 -2.094
0.0004 -2.092 0.0003 -2.085
0.0005 -2.080 0.0004 -2.069
0.0002 -2.067 0.0003 -2.065
0.0003 -2.055 0.0005 -2.052
0.0004 -2.044 0.0003 -2.022
0.0003 -2.033 0.0001 -2.019
0.0003 -2.021 0.0003 -2.020
0.0002 -2.011 0.0001 -2.005
0.0003 -1.984 0.0013 -1.985
0.0004 -1.967 0.0006 -1.968
0.0003 -1.922 0.0008 -1.923
0.0013 -1.944 0.0004 -1.939
0.0017 -1.907 0.0005 -1.907
0.0005 -1.881 0.0008 -1.891
0.0017 -1.866 0.0015 -1.869
0.0007 -1.852 0.0011 -1.853
0.0012 -1.826 0.0013 -1.833
0.0008
0.0006
0.0010
0.0013
0.0008
0.0010
0.0014
0.0011
0.0011
0.0011
0.0008
0.0007
0.0007
0.0008
0.0010
0.0015
0.0016
0.0012
0.0017
0.0011
0.0011
0.0010
0.0014
0.0016
0.0003
0.0011
0.0004
0.0003
0.0009
0.0005
0.0007
0.0004
0.0006
0.0007
0.0006
0.0001
0.0003
0.0003
0.0004
0.0003
0.0003
0.0002
0.0003
0.0003
0.0003
0.0004
0.0007
0.0003
0.0006
0.0006
0.0004
0.0006
0.0004
0.0003
0.0002
0.0003
0.0004
0.0003
0.0003
0.0003
0.0002
0.0003
0.0004
0.0003
0.0008
0.0004
0.0004
0.0008
0.0005
0.0007
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
3.60
-2.276
-2.264
-2.256
-2.247
-2.231
-2.214
-2.198
-2.189
-2.185
-2.171
-2.132
-2.135
-2.137
-2.103
-2.150
-2.116
-2.103
-2.089
-2.076
-2.064
-2.051
-2.039
-2.028
-2.016
-2.004
-1.992
-1.971
-1.951
-1.907
-1.930
-1.884
-1.869
-1.855
-1.839
-1.808
-2.289
-2.283
-2.275
-2.261
-2.248
-2.235
-2.222
-2.208
-2.196
-2.184
-2.160
-2.145
-2.136
-2.125
-2.172
-2.114
-2.102
-2.087
-2.076
-2.064
-2.051
-2.039
-2.026
-2.014
-2.004
-1.993
-1.968
-1.935
-1.895
-1.925
-1.877
-1.849
-1.848
-1.807
-1.790
0.0003
0.0001
0.0003
0.0003
0.0004
0.0001
0.0001
0.0003
0.0002
0.0002
0.0003
0.0010
0.0007
0.0005
0.0004
0.0004
0.0002
0.0007
0.0005
0.0003
0.0005
0.0003
0.0007
0.0007
0.0003
0.0003
0.0007
0.0014
0.0018
0.0011
0.0012
0.0006
0.0014
0.0007
0.0006
0.0005
0.0009
0.0011
0.0011
0.0009
0.0009
0.0015
0.0007
0.0011
0.0004
0.0011
0.0007
0.0011
0.0012
0.0011
0.0012
0.0012
0.0007
0.0011
0.0011
0.0011
0.0009
0.0006
0.0007
0.0017
0.0012
0.0010
0.0008
0.0009
0.0022
0.0024
0.0006
0.0016
0.0011
0.0008
S36
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0007
0.0017
0.0011
0.0009
0.0011
0.0016
0.0022
0.0010
0.0010
0.0011
0.0008
0.0019
0.0002
0.0012
0.0012
0.0001
0.0002
0.0003
0.0003
0.0003
0.0004
0.0003
0.0003
0.0002
0.0005
0.0008
0.0007
0.0003
0.0013
0.0007
0.0015
0.0012
0.0006
0.0008
0.0011
-2.289
-2.263
-2.261
-2.250
-2.248
-2.221
-2.203
-2.193
-2.168
-2.167
-2.157
-2.134
-2.137
-2.096
-2.149
-2.111
-2.102
-2.088
-2.076
-2.063
-2.049
-2.037
-2.028
-2.015
-2.003
-1.994
-1.970
-1.950
-1.910
-1.929
-1.892
-1.874
-1.841
-1.836
-1.803
0.0006
0.0007
0.0006
0.0007
0.0002
0.0009
0.0016
0.0007
0.0008
0.0010
0.0009
0.0023
0.0005
0.0021
0.0007
0.0013
0.0004
0.0006
0.0005
0.0004
0.0005
0.0005
0.0003
0.0003
0.0007
0.0004
0.0008
0.0004
0.0006
0.0009
0.0003
0.0004
0.0012
0.0009
0.0009
-2.275
-2.269
-2.258
-2.247
-2.233
-2.220
-2.205
-2.194
-2.184
-2.168
-2.149
-2.133
-2.121
-2.110
-2.157
-2.100
-2.086
-2.074
-2.064
-2.049
-2.036
-2.023
-2.017
-2.001
-1.991
-1.980
-1.956
-1.939
-1.905
-1.916
-1.880
-1.852
-1.834
-1.819
-1.818
Points
R1
R2
2.30 1.64
2.30 1.66
2.30 1.68
2.30 1.72
2.30 1.76
2.30 1.80
2.30 1.84
2.30 1.88
2.30 1.92
2.30 1.96
2.30 2.00
2.30 2.04
2.30 2.08
2.30 2.12
2.30 2.16
2.30 2.20
2.30 2.25
2.30 2.30
2.30 2.35
2.30 2.40
2.30 2.45
2.30 2.50
2.30 2.55
2.30 2.60
2.30 2.65
2.30 2.70
2.30 2.80
2.30 2.90
2.30 3.00
2.30 3.10
2.30 3.20
2.30 3.30
2.30 3.40
2.30 3.50
2.30 3.60
Corrections from
Case A
-2.555 0.0002
-2.547 0.0003
-2.541 0.0002
-2.526 0.0003
-2.513 0.0002
-2.498 0.0003
-2.486 0.0002
-2.474 0.0002
-2.461 0.0004
-2.449 0.0003
-2.425 0.0003
-2.413 0.0002
-2.402 0.0004
-2.391 0.0004
-2.382 0.0001
-2.436 0.0003
-2.368 0.0003
-2.355 0.0003
-2.342 0.0002
-2.329 0.0003
-2.315 0.0005
-2.306 0.0000
-2.289 0.0007
-2.280 0.0005
-2.268 0.0006
-2.258 0.0003
-2.233 0.0008
-2.216 0.0005
-2.169 0.0007
-2.193 0.0005
-2.148 0.0011
-2.132 0.0008
-2.110 0.0015
-2.088 0.0014
-2.073 0.0008
Fixman
Case B
-2.554
-2.547
-2.542
-2.528
-2.514
-2.501
-2.488
-2.475
-2.463
-2.450
-2.426
-2.415
-2.403
-2.393
-2.382
-2.438
-2.368
-2.355
-2.342
-2.329
-2.317
-2.304
-2.292
-2.281
-2.270
-2.255
-2.235
-2.214
-2.169
-2.191
-2.152
-2.132
-2.114
-2.095
-2.082
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0005 -2.554 0.0004 -2.555
0.0003 -2.548 0.0002 -2.548
0.0002 -2.540 0.0003 -2.541
0.0001 -2.526 0.0003 -2.527
0.0001 -2.513 0.0003 -2.512
0.0001 -2.499 0.0004 -2.500
0.0001 -2.486 0.0005 -2.487
0.0001 -2.473 0.0006 -2.474
0.0001 -2.460 0.0005 -2.461
0.0002 -2.448 0.0006 -2.448
0.0003 -2.424 0.0004 -2.424
0.0001 -2.413 0.0004 -2.413
0.0001 -2.401 0.0004 -2.403
0.0001 -2.389 0.0005 -2.393
0.0001 -2.382 0.0002 -2.380
0.0002 -2.436 0.0005 -2.438
0.0002 -2.368 0.0002 -2.367
0.0001 -2.355 0.0002 -2.354
0.0001 -2.341 0.0004 -2.341
0.0006 -2.329 0.0006 -2.328
0.0003 -2.318 0.0002 -2.318
0.0005 -2.304 0.0004 -2.306
0.0005 -2.292 0.0005 -2.294
0.0004 -2.282 0.0003 -2.282
0.0004 -2.269 0.0005 -2.270
0.0007 -2.258 0.0005 -2.260
0.0003 -2.237 0.0005 -2.237
0.0008 -2.212 0.0015 -2.218
0.0009 -2.175 0.0005 -2.178
0.0007 -2.192 0.0011 -2.196
0.0004 -2.140 0.0013 -2.156
0.0007 -2.130 0.0007 -2.140
0.0009 -2.109 0.0008 -2.122
0.0005 -2.086 0.0005 -2.099
0.0010 -2.081 0.0007 -2.085
0.0003
0.0002
0.0003
0.0002
0.0004
0.0003
0.0002
0.0004
0.0003
0.0002
0.0003
0.0003
0.0001
0.0002
0.0003
0.0003
0.0004
0.0002
0.0005
0.0006
0.0002
0.0002
0.0004
0.0002
0.0005
0.0001
0.0003
0.0001
0.0003
0.0004
0.0003
0.0004
0.0004
0.0003
0.0005
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
2.35
-2.542
-2.535
-2.528
-2.514
-2.499
-2.486
-2.474
-2.461
-2.448
-2.436
-2.411
-2.400
-2.388
-2.377
-2.369
-2.423
-2.355
-2.342
-2.329
-2.316
-2.304
-2.293
-2.280
-2.267
-2.255
-2.244
-2.222
-2.197
-2.157
-2.177
-2.137
-2.122
-2.102
-2.076
-2.058
-2.543
-2.535
-2.529
-2.515
-2.501
-2.488
-2.474
-2.462
-2.449
-2.437
-2.414
-2.402
-2.391
-2.379
-2.368
-2.425
-2.355
-2.342
-2.328
-2.317
-2.303
-2.292
-2.278
-2.268
-2.256
-2.243
-2.221
-2.196
-2.159
-2.181
-2.137
-2.120
-2.099
-2.072
-2.061
0.0001
0.0002
0.0001
0.0001
0.0003
0.0001
0.0003
0.0003
0.0002
0.0002
0.0002
0.0002
0.0002
0.0004
0.0002
0.0001
0.0003
0.0002
0.0007
0.0003
0.0005
0.0006
0.0007
0.0005
0.0009
0.0010
0.0008
0.0012
0.0013
0.0006
0.0018
0.0008
0.0011
0.0020
0.0014
0.0001
0.0003
0.0003
0.0002
0.0004
0.0004
0.0002
0.0001
0.0003
0.0004
0.0004
0.0002
0.0002
0.0003
0.0004
0.0002
0.0002
0.0005
0.0002
0.0003
0.0003
0.0004
0.0003
0.0005
0.0002
0.0006
0.0007
0.0004
0.0005
0.0008
0.0009
0.0003
0.0004
0.0015
0.0007
1.64
1.66
1.68
1.72
1.76
1.80
1.84
1.88
1.92
1.96
2.00
2.04
2.08
2.12
2.16
2.20
2.25
2.30
2.35
2.40
2.45
2.50
2.55
2.60
2.65
2.70
2.80
2.90
3.00
3.10
3.20
3.30
3.40
3.50
3.60
0.0002
0.0003
0.0003
0.0002
0.0004
0.0006
0.0002
0.0003
0.0003
0.0003
0.0005
0.0004
0.0005
0.0006
0.0001
0.0003
0.0002
0.0002
0.0003
0.0002
0.0002
0.0002
0.0005
0.0007
0.0008
0.0005
0.0007
0.0010
0.0006
0.0015
0.0008
0.0005
0.0008
0.0015
0.0010
-2.542
-2.535
-2.528
-2.514
-2.500
-2.487
-2.473
-2.461
-2.448
-2.437
-2.411
-2.400
-2.388
-2.377
-2.369
-2.423
-2.356
-2.341
-2.329
-2.317
-2.304
-2.292
-2.278
-2.267
-2.253
-2.243
-2.219
-2.190
-2.161
-2.181
-2.139
-2.112
-2.100
-2.082
-2.066
0.0002
0.0002
0.0003
0.0002
0.0001
0.0003
0.0003
0.0001
0.0004
0.0005
0.0004
0.0004
0.0003
0.0004
0.0001
0.0005
0.0002
0.0006
0.0003
0.0003
0.0004
0.0005
0.0004
0.0008
0.0009
0.0007
0.0012
0.0013
0.0009
0.0003
0.0009
0.0014
0.0013
0.0010
0.0009
-2.542
-2.535
-2.527
-2.514
-2.499
-2.487
-2.473
-2.462
-2.448
-2.436
-2.412
-2.401
-2.389
-2.379
-2.368
-2.424
-2.355
-2.341
-2.329
-2.317
-2.304
-2.292
-2.280
-2.269
-2.258
-2.246
-2.222
-2.204
-2.163
-2.182
-2.140
-2.128
-2.107
-2.083
-2.070
Points
R1
R2
3.70 1.64
3.70 1.66
3.70 1.68
3.70 1.72
3.70 1.76
3.70 1.80
3.70 1.84
3.70 1.88
3.70 1.92
3.70 1.96
3.70 2.00
3.70 2.04
3.70 2.08
3.70 2.12
3.70 2.16
3.70 2.20
3.70 2.25
3.70 2.30
3.70 2.35
3.70 2.40
3.70 2.45
3.70 2.50
3.70 2.55
3.70 2.60
3.70 2.65
3.70 2.70
3.70 2.80
3.70 2.90
3.70 3.00
3.70 3.10
3.70 3.20
3.70 3.30
3.70 3.40
3.70 3.50
3.70 3.60
S37
Corrections from
Case A
-2.253 0.0017
-2.252 0.0009
-2.240 0.0014
-2.231 0.0025
-2.211 0.0009
-2.206 0.0005
-2.180 0.0016
-2.175 0.0012
-2.167 0.0008
-2.133 0.0001
-2.143 0.0006
-2.114 0.0010
-2.114 0.0016
-2.086 0.0011
-2.138 0.0012
-2.099 0.0003
-2.086 0.0002
-2.072 0.0006
-2.058 0.0005
-2.047 0.0004
-2.033 0.0005
-2.023 0.0003
-2.011 0.0005
-1.999 0.0004
-1.985 0.0008
-1.974 0.0011
-1.956 0.0004
-1.933 0.0004
-1.893 0.0006
-1.914 0.0006
-1.863 0.0024
-1.853 0.0009
-1.837 0.0014
-1.814 0.0013
-1.795 0.0008
Fixman
Case B
-2.273
-2.266
-2.258
-2.242
-2.231
-2.217
-2.202
-2.189
-2.180
-2.168
-2.143
-2.127
-2.121
-2.106
-2.152
-2.094
-2.086
-2.072
-2.053
-2.045
-2.036
-2.022
-2.010
-1.995
-1.989
-1.972
-1.956
-1.927
-1.891
-1.908
-1.866
-1.850
-1.821
-1.800
-1.779
determinant ave+/-std (kcal/mol)
Case C
Case D
0.0002 -2.255 0.0010 -2.240
0.0005 -2.248 0.0009 -2.251
0.0005 -2.242 0.0010 -2.242
0.0011 -2.236 0.0011 -2.226
0.0004 -2.215 0.0009 -2.217
0.0005 -2.199 0.0009 -2.202
0.0002 -2.202 0.0008 -2.181
0.0006 -2.171 0.0018 -2.169
0.0004 -2.163 0.0010 -2.163
0.0003 -2.150 0.0013 -2.150
0.0003 -2.123 0.0015 -2.124
0.0013 -2.112 0.0019 -2.115
0.0002 -2.115 0.0006 -2.109
0.0007 -2.109 0.0004 -2.096
0.0011 -2.140 0.0010 -2.139
0.0008 -2.098 0.0005 -2.079
0.0002 -2.086 0.0003 -2.069
0.0002 -2.070 0.0009 -2.050
0.0015 -2.060 0.0003 -2.049
0.0009 -2.047 0.0004 -2.018
0.0001 -2.034 0.0005 -2.013
0.0005 -2.007 0.0020 -1.991
0.0008 -2.012 0.0002 -1.992
0.0006 -2.000 0.0003 -1.972
0.0005 -1.987 0.0006 -1.959
0.0019 -1.978 0.0002 -1.951
0.0001 -1.956 0.0004 -1.933
0.0026 -1.929 0.0010 -1.901
0.0008 -1.891 0.0012 -1.871
0.0013 -1.913 0.0008 -1.889
0.0014 -1.876 0.0006 -1.847
0.0004 -1.852 0.0012 -1.841
0.0017 -1.830 0.0023 -1.810
0.0016 -1.816 0.0010 -1.789
0.0004 -1.781 0.0015 -1.788
0.0005
0.0010
0.0012
0.0013
0.0016
0.0005
0.0007
0.0017
0.0005
0.0010
0.0011
0.0011
0.0012
0.0010
0.0010
0.0013
0.0010
0.0008
0.0012
0.0009
0.0016
0.0006
0.0016
0.0007
0.0015
0.0009
0.0009
0.0004
0.0015
0.0007
0.0012
0.0012
0.0003
0.0004
0.0021
References
[1] Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. J. Chem. Theory Comput. 2008, 4,
435–447.
[2] Bolhuis, P. G.; Chandler, D.; Dellago, C.; Geissler, P. L. Annu. Rev. Phys. Chem. 2002, 53,
291–318.
[3] Van Erp, T. S.; Moroni, D.; Bolhuis, P. G. J. Chem. Phys. 2003, 118, 7762–7774.
[4] Li, W.; Gräter, F. J. Am. Chem. Soc. 2010, 132, 16790–16795.
S38