We describe the development, testing, and application of the new hybrid method combining discrete molecular dynamics and quantum mechanical calculations, QM/DMD, for metallo-protein modeling. QM/DMD is efficient, and features the aggressive sampling of the entire protein including the backbone, and the accurate description of the electronic structure of the active site. We demonstrate the capabilities of QM/DMD by addressing two significantly different problems: I) We consider Rubredoxin and its mutants, and predict structures for the two possible oxidation states, as well as the effect of mutations on the RedOx potential II) We address the catalytic cycle of catechol-o-methyltransferase (COMT), an enzyme involved in the inactivation of the catecholamine neurotransmitters, as a function of the nature of the bound metal.

Modeling of metallo-enzymes: Combining quantum mechanical calculations with discrete molecular dynamic

243rd National Meeting (2012)

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