Expanding the view of proton pumping in cytochrome c oxidase through computer simulation

► Reactive molecular dynamics studies of proton transport in CcO are reported. ► The multi-state empirical valence bond (MS-EVB) methodology is used. ► Proton shuttling mechanism through water molecules in CcO was studied. ► Proton transport in the D-channel and the hydrophobic cavity past E286 were studied. ► We provide molecular insight how the electronic state modulates the proton transport.