Computer Simulation of Explicit Proton Translocation in Cytochrome c Oxidase: the D-pathway

TitleComputer Simulation of Explicit Proton Translocation in Cytochrome c Oxidase: the D-pathway
Publication TypeJournal Article
Year of Publication2005
AuthorsXu, J, Voth, GA
JournalProc Natl Acad Sci U S A
KeywordsAnimals Biophysics/*methods Cattle Computer Simulation Crystallography, Molecular Models, Statistical Mutagenesis Protons Serine/chemistry Static Electricity Thermodynamics Time Factors Water/chemistry, X-Ray Electron Transport Complex IV/*chemistry Glutamic Acid/chemistry Mitochondria/metabolism Models

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.