Ab initio molecular dynamics studies of flavocytochrome b2 reduction

The ab initio Car-Parrinello molecular dynamics simulations approach to the study of reactive events may prove to be a powerful tool to gain insights into the mechanism of enzyme-catalysed reactions, which are not readily accessible to the experimentalist. In order to test whether this approach is feasible in the case of flavin-dependent enzymes, we have initiated a series of ab initio molecular dynamics studies of -amino and -hydroxy acid oxidation in D-amino acid oxidase (DAAO) and L-lactate dehydrogenase (flavocytochrome b2, Fcb2) active site models. We here present the modeling of Fcb2-catalysed L-lactate oxidation, in which the critical step is represented by the building of the Michaelis complex model in light of the possible multiple binding modes of the substrate and of the possible conformational changes of Fcb2 during catalysis..