Dynamic networks in complex biomolecules
Hydrogen-bond networks in proton transfer and chemo-mechanical coupling
S. Adam, K. Buzar, F. Guerra, K. Karathanou, A.Molecular dynamics simulations of photosystem
N. Bondar, Department of Physics, Freie Universität II pose the challenge of describing accurately the
Berlin, Theoretical Molecular Biophysics Group
numerous cofactor and special lipid molecules, for
which parameters may need to be revised or derived.
We plan here work on enhancing the current descripIn Short
tion of selected cofactor regions of photosystem II.
• Long-distance proton transfer occurs via protein/water hydrogen-bonded networks
• Assembly of hydrogen-bonded networks couples
to protein and water dynamics, and to the protonation state
• Channelrhodopsins and photosystem II are model
systems for protonation-coupled protein and water
dynamics
• Analysis of dynamic hydrogen-bond networks in
complex biomolecular environments requires efficient, specialized tools
• Accurate computations of photosystem II requires reliable force-field parameters for cofactor
Figure 1: Molecular graphics of a photosystem II monomer. Promolecules
teins chains are shown as gray ribbons, cofactor and special
Long-distance proton transfer reactions in proteins
involve the transfer of a proton from the donor to
the acceptor group via intervening hydrogen-bond
networks. These hydrogen bond networks can be
rather dynamic, that is, they form and break during
the functioning of the protein. To identify dynamic
hydrogen-bond networks and characterize their dynamics in a complex biomolecular environment, we
need all-atom simulations on time scales appropriate for sampling relevant protein and water motions,
and efficient tools to analyze large data sets resulting
fron the simulations. We study two model systems: i)
photosystem II (Fig. 1), a protein/cofactor machinery
that splits water molecules; ii) channelrhodopsins,
which are retinal proteins (Fig. 2) that can be used
in optogenetics applications.
During previous bec00063 allocations we have
studied extensively the molecular dynamics of a subunit of PsbO, a soluble subunit of photosystem II
[2,6,7], and worked on parametrizations of selected
cofactor molecules [8]. These achievements provide
the foundation for work on understanding the dynamics of photosystem II. An important step towards this
aim is to develop tools for efficient analyses of large
data sets, as anticipated for studies of the complete
photosystem II dimer (Fig. 3). We develop and test
data analysis tools using smaller systems - the PsbO
subunit of photosystem II, or the SecA protein motor
(Fig. 4).
lipid molecules as van der Waals spheres with carbon atoms
colored cyan, nitrogen - blue, oxygen - red, and sulphur - yellow.
The image is based on the crystal structure from refs. [4,5]. All
molecular graphics were prepared with VMD [3].
In channelrhodopsins, proton-transfer reactions
occur after the retinal chromophore has undergone
photo-isomerization from all-trans to 13-cis. To find
out how proton transfer occurs, we augment classical molecular dynamics simulations of channelrhodopsin variants with combined quantum mechanical/ molecular mechanical (QM/MM) computations
that allow us to describe explicitly breaking and forming of chemical bonds.
Figure 2: Channelrhodopsin dimer in a hydrated lipid membrane
environment. The protein chains are shown as yellow cartoons.
Lipid molecules, the retinal cofactors and water molecules, are
shown as van der Waals hydrogen atoms of waters - white. The
starting protein structure was taken from ref. [1]
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Figure 3: Protein and cofactor interactions in the photosystem II dimer. The PsbO protein is shown as orange ribbons.
Data analysis methods developed here for SecA WWW
(Fig. 4) may become useful for efficient analyses http://www.physik.fu-berlin.de/en/
of hydrogen bonding at the surface of much larger einrichtungen/ag/ag-bondar/
systems, such as the photosystem II dimer.
More Information
[1] H.E.. Kato, et. al, Nature 482, 369 (2012). doi:
10.1038/nature108705
[2] S. Lorch, S. Capponi, F. Pieront, A.-N. Bondar, J. Phys. Chem B 1837, 119 (2015). doi:
10.1021/acs.jpcb.5b06594
[3] W. Humphrey, A. Dalke, K. Schulten, J. Molec.
Graphics 14, 33 (1996).
[4] Y.. Umena, K. Shen, J.-R. Kamiya Nature 473,
55 (2011). doi:10.1038/nature09913.
[5] M.. Suga, F. Akita, K. Hirata, G. Ueno, H.
Murakami, Y. Nakajima, T. Shimizu, K. Yamashita, M. Yamamoto, M. Yamamoto, H.
Ago, J.-R. Shen Nature 517, 99 (2015). doi:
10.1038/nature13991.
[6] M.. Bommer, A-N. Bondar, A. Zouni, H.
Dobbeck, H. Dau, Biochemistry 55, 4626
(2016). doi:10.1021/acs.biochem.6b00441.
Figure 4: Surface representation of the SecA protein motor based
on a coordinate snapshot from a molecular dynamics simulation.
The adenosine diphosphate molecule is shown as yellow bonds,
and the magnesium ion as a pink sphere. The first hydration shell
of the protein is shown in light blue.
In summary, the new proposal aims to contribute
to our general understanding of long-distance proton
transfers in channelrhodopsins and photosystem II.
We perform prolonged classical molecular dynamics
simulations to probe protein dynamics, and QM/MM
computations for proton transfer reactions. These
computations are augmented by the development
of new tools for the efficient analysis of large data
sets.
[7] C. delVal, A-N. Bondar, Biochim. Biophys. Acta 1858, 432 (2017). doi:
10.1016/j.bbabio.2017.03.004.
[8] F. Guerra, S. Adam, A-N. Bondar,
Biochim. Biophys. Acta 58, 30 (2015). doi:
10.1016/j.jmgm.2015.03.001.
Funding
Project C4, DFG Collaboration Research Center
SFB 1078, Protonation Dynamics in Protein Function; Excellence Initiative of the German Federal and
State Governments provided via the Freie Universität Berlin.
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