| Vectorial proton translocation through membranes is a fundamental energy conversion process in biological cells. In this dissertation, the molecular mechanisms of proton translocation and pumping in the native cytochrome c oxidase (CcO) enzyme and mutants are investigated by a combination of classical molecular dynamics (MD) and the multi-state empirical valence bond (MS-EVB) methodology. Attention was focused on the D-pathway as well as the region between and above heme a and heme a3 where the proton exit channel initiates. Dynamical properties and the potential of mean force of proton propagation through the channels were calculated in order to provide a detailed mechanistic picture of proton conduction. Also discussed are key elements in the proton translocation and pumping mechanism, including the role of bound water molecules, conserved amino acids, heme propionates and redox metal sites. |
