Parametrization of Molybdenum Cofactors for the AMBER Force Field

Pedro Ferreira, Nuno M.F.S.A. Cerqueira, NatérciaF. Brás, Pedro A. Fernandes, Maria J. Ramos

Index: 10.1021/acs.jctc.8b00137

Full Text: HTML

Abstract

Molybdenum-containing enzymes have been receiving significant attention from the scientific community since they participate in important biological processes and in the global biogeochemical cycles of carbon, nitrogen, and sulfur. Molecular modeling studies of these metalloproteins with classical force fields are, however, often hampered by the “missing parameter” problem. In this article, a set of parameters have been determined for the AMBER force field from nine different molybdenum cofactors. All of these cofactors were optimized and parametrized using a bonded model approach. All of the bonds and angles involving the Mo ion were parametrized. The Restrained Electrostatic Potential charges of the coordination sphere of each cofactor were also determined. Finally, we demonstrated the stability of our parameters in a showcase of nine enzymes. The parameters presented in this work provide a valuable resource for the molecular simulation community as they extend the range of metal ions that can be studied using classical approaches while also providing a starting point for subsequent parametrization of similar metal centers. All of the developed parameters can be found in the Supporting Information.