Higher Protonation States of Vanadium Chloroperoxidase: A QM/MM Study with an Atom-in-Molecules Analysis

Earlier QM/MM studies of the resting state of vanadium chloroperoxidase (VCPO) focused on the diprotonated forms of the vanadate cofactor. But recent arguments have been made that vanadate is in a quadprotonated form at pH 6.3. In this regard, an extensive QM/MM study on various possible protonation states of VCPO has been carried out. A large decrease in energy (about 200 kcal/mol per additional proton) has been found while going from mono-, di-, tri- to quad- protonated states. Separate QM studies on the isolated cofactor shows a similar trend in energies for different protonation states. A natural bond orbital (NBO) study shows extensive delocalization in quadprotonated states, and an Atoms-in-Molecules (AIM) study predicts some important hydrogen bonding not reported earlier.