Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics.
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Supplementary Information
Theoretical studies of energetics and binding isotope effects of binding a
triazole-based inhibitor to HIV-1 reverse transcriptase
a
A. Krzemińska, K. P. Świderek
a,b
and P. Paneth
a*
Figure S1. Structural formulas of reverse transcrpitase nucleoside (NRTIs) and non-nucleoside
(NNRTIs) inhibitors with new proposed triazole-based ligand.
Table S1. Computed heavy atoms BIEs for L-1 extracted from allosteric cavity and RNase H active site.
Comparison of the arithemtic mean of the 121 combinations of water and enzyme complexes,
variant 1, with the quotient of average isotopic fractionaction factors evaluated for the 11 water
complexes and idependently for the 11 enzyme complexes, variant 2.
34
33
1
32
30
31
27
22
19
6
23
12 13
3
4
26
25
17
2
5
10
7
28
24
11
14
18
20
8
16
9
15
21
29
atom
15
N
N
15
N
15
N
15
N
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
18
O
18
O
18
O
34
S
34
S
34
S
37
Cl
15
No.
1
2
4
10
21
3
5
7
8
11
12
13
14
15
16
22
23
24
25
26
27
28
29
30
32
33
34
9
19
20
6
18
31
17
Allosteric cavity
variant 1
0.997
0.999
1.001
0.999
1.003
0.998
0.998
1.001
1.000
1.000
1.000
1.003
1.004
1.001
1.000
0.999
1.002
1.003
1.001
0.997
0.997
1.004
1.002
0.997
0.998
0.995
0.996
1.000
1.001
1.016
0.997
1.008
1.001
1.002
Allosteric cavity
variant 2
0.997
0.999
1.001
0.999
1.003
0.998
0.998
1.001
1.000
1.000
1.000
1.003
1.004
1.001
1.000
0.999
1.002
1.003
1.001
0.997
0.997
1.004
1.002
0.997
0.998
0.995
0.996
1.000
1.001
1.016
0.997
1.008
1.001
1.002
RNase H active site
variant 1
0.9967023938
0.998
1.000
0.998
1.000
1.001
0.999
0.998
0.997
1.001
1.000
1.001
1.001
1.001
1.000
0.999
1.000
1.003
1.005
1.003
1.001
0.998
1.009
0.999
1.001
1.004
1.003
0.994
0.997
0.988
0.997
0.999
0.998
1.001
RNase H active site
variant 2
0.996701989
0.998
1.000
0.998
1.000
1.001
0.999
0.998
0.997
1.001
1.000
1.001
1.001
1.001
1.000
0.999
1.000
1.003
1.005
1.003
1.001
0.998
1.009
0.999
1.001
1.004
1.003
0.994
0.997
0.988
0.997
0.999
0.998
1.001
Table S2. Comparison of BIEs computed with and without translation and rotation functions, eq1 and
eq2 respecively, using the arithemtic mean of the 121 combinations of water and enzyme complexes.
34
33
1
32
30
31
27
22
19
6
23
24
12 13
3
4
26
25
17
2
5
28
10
7
11
14
18
20
8
16
15
9
21
29
atom
15
N
N
15
N
15
N
15
N
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
13
C
18
O
18
O
18
O
34
S
34
S
34
S
37
Cl
15
No.
1
2
4
10
21
3
5
7
8
11
12
13
14
15
16
22
23
24
25
26
27
28
29
30
32
33
34
9
19
20
6
18
31
17
Allosteric cavity
eq1
0.997
0.999
1.001
0.999
1.003
0.998
0.998
1.001
1.000
1.000
1.000
1.003
1.004
1.001
1.000
0.999
1.002
1.003
1.001
0.997
0.997
1.004
1.002
0.997
0.998
0.995
0.996
1.000
1.001
1.016
0.997
1.008
1.001
1.002
Allosteric cavity
eq2
0.997
0.999
1.001
0.999
1.003
0.998
0.998
1.001
1.000
1.000
1.000
1.003
1.004
1.001
0.443
0.997
0.996
0.995
0.998
0.999
0.997
0.997
1.001
1.003
1.002
1.002
1.004
1.000
1.001
1.016
0.997
1.008
1.001
1.002
RNase H active site
eq1
0.997
0.998
1.000
0.998
1.000
1.001
0.999
0.998
0.997
1.001
1.000
1.001
1.001
1.001
1.000
0.999
1.000
1.003
1.005
1.003
1.001
0.998
1.009
0.999
1.001
1.004
1.003
0.994
0.997
0.988
0.997
0.999
0.998
1.001
RNase H active site
eq2
0.997
0.998
1.000
0.998
1.000
1.001
0.999
0.998
0.997
1.001
1.000
1.001
1.001
1.001
1.000
0.999
1.003
1.004
1.001
0.999
1.001
1.003
1.005
1.003
1.000
1.009
0.998
0.994
0.997
0.988
0.997
0.999
0.998
1.001
Figure S2. The average distances reported in Å with their standard deviation obtained for eleven
localized structures of L-1 bounded in allosteric cavity prepared to BIEs calculations.
Figure S3. Evolution of key disntances in allosteric cavity during last 20 ps of QMMM MD. Structures
from last 20ps were extracted to further analysis and BIEs calculations.
Figure S4. The average distances reported in Å with their standard deviation obtained for eleven
localized structures of L-1 bounded in RNase H active site prepared to BIEs calculations.
Figure S5. Evolution of key disntances in RNase H active site during last 20 ps of QMMM MD.
Structures from last 20ps were extracted to further analysis and BIEs calculations.