title: Computer simulation of explicit proton translocation in cytochrome c oxidase: the D-pathway.
abstract: Proton translocation in the D-pathway of cytochrome c oxidase has been studied by a combination of classical molecular dynamics and the multistate empirical valence bond methodology. This approach allows for explicit Grotthuss proton hopping between water molecules. According to mutagenesis experiments, the role of proton donor/acceptor along the D-pathway is carried by the highly conserved residue Glu-242. The present multistate empirical valence bond simulations indicate that the protonation/deprotonation state of Glu-242 is strongly coupled to the distance of proton propagation in the D-pathway. The proton was seen to travel the full length of the D-pathway when Glu-242 was deprotonated; however, it was trapped halfway along the path when Glu-242 was protonated. Further investigation in terms of both proton dynamical properties and free energy calculations for the pathway of proton transport provides evidence for a two-step proton transport mechanism in the D-pathway.
authors.affiliation: Department of Chemistry and Center for Biophysical Modeling and Simulation, 315 South 1400 East Room 2020, University of Utah, Salt Lake City, UT 84112-0850, USA.
authors.forename: Jiancong
authors.initials: J
authors.lastname: Xu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D000818:Animals; D001703:Biophysics / Q000379:methods*; D002417:Cattle; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003576:Electron Transport Complex IV / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D015233:Models, Statistical; D016296:Mutagenesis; D011522:Protons; D012694:Serine / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D011522:Protons; D014867:Water; D018698:Glutamic Acid; D012694:Serine; D003576:Electron Transport Complex IV