First-principles molecular dynamics study of proton transfer mechanism in bovine cytochromec oxidase

Abstract

Density functional based first-principles molecular dynamics calculations,performed on a model system extracted from the bovine cytochromec oxidase, have been performed in an attempt to inspect the proton transfer mechanism across apeptide group. Our model system includes the specific Tyr440-Ser441 peptide groupinvolved in a novel proton transfer path and shows that the Y440-S441 enol peptide group[–C(OH) = N–], which is a structural isomer of a keto form [–CO–NH–], is the product of the deprotonationof an imidic acid [–C(OH)–NH–] occurring in the vicinity of the deprotonatedaspartic acid residue. For the subsequent enol-to-keto tautomerization, a directH+ transfer path in the Y440-S441 peptide group has been identified, in which the transitionstate takes a distorted four-membered ring structure.