Proton transfer at metal sites in proteins studied by quantum mechanical free-energy perturbations
Catalytic metal sites in enzymes frequently have second-sphere carboxylate groups that neutralize the charge of the site and share protons with first-sphere ligands. This gives rise to an ambiguity concerning the position of this proton, which has turned out to be hard to settle with experimental, as well as theoretical, methods. We study three such proton-transfer reactions in two proteins and sh