title: Water molecules and hydrogen-bonded networks in bacteriorhodopsin--molecular dynamics simulations of the ground state and the M-intermediate.
abstract: Protein crystallography provides the structure of a protein, averaged over all elementary cells during data collection time. Thus, it has only a limited access to diffusive processes. This article demonstrates how molecular dynamics simulations can elucidate structure-function relationships in bacteriorhodopsin (bR) involving water molecules. The spatial distribution of water molecules and their corresponding hydrogen-bonded networks inside bR in its ground state (G) and late M intermediate conformations were investigated by molecular dynamics simulations. The simulations reveal a much higher average number of internal water molecules per monomer (28 in the G and 36 in the M) than observed in crystal structures (18 and 22, respectively). We found nine water molecules trapped and 19 diffusive inside the G-monomer, and 13 trapped and 23 diffusive inside the M-monomer. The exchange of a set of diffusive internal water molecules follows an exponential decay with a 1/e time in the order of 340 ps for the G state and 460 ps for the M state. The average residence time of a diffusive water molecule inside the protein is approximately 95 ps for the G state and 110 ps for the M state. We have used the Grotthuss model to describe the possible proton transport through the hydrogen-bonded networks inside the protein, which is built up in the picosecond-to-nanosecond time domains. Comparing the water distribution and hydrogen-bonded networks of the two different states, we suggest possible pathways for proton hopping and water movement inside bR.
authors.affiliation: Institute for Structural Biology (IBI-2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Sergei
authors.initials: S
authors.lastname: Grudinin
authors.forename: Georg
authors.initials: G
authors.lastname: Büldt
authors.forename: Valentin
authors.initials: V
authors.lastname: Gordeliy
authors.forename: Artur
authors.initials: A
authors.lastname: Baumgaertner
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry*; D001692:Biological Transport; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004058:Diffusion; D019281:Dimerization; D006217:Halobacterium / Q000378:metabolism; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D010713:Phosphatidylcholines / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D012984:Software; D013997:Time Factors; D014867:Water / Q000737:chemistry*
chemical_list: D010713:Phosphatidylcholines; D011522:Protons; D014867:Water; D001436:Bacteriorhodopsins; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
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