Computational Modeling of the Interaction of Molecular Oxygen with the Flavin-dependent Enzyme RutA

Abstract

Supercomputer molecular modeling methods are applied to characterize structure and dynamics of the flavin-dependent enzyme RutA in the complex with molecular oxygen. Following construction of a model protein system, molecular dynamics (MD) simulations were carried out using either classical force field interaction potentials or the quantum mechanics/molecular mechanics (QM/MM) potentials. Several oxygen-binding pockets in the protein cavities were located in these simulations. The QM/MM-based MD calculations rely on the interface between the quantum chemistry package TeraChem and the MD package NAMD. The results show a stable localization of the oxygen molecule in the enzyme active site. Static QM/MM calculations carried out with two different packages, NWChem and TURBOMOLE, allowed us to establish the structure of the RutA-O2 complex. Biochemical perspectives of the hallmark reaction of incorporating oxygen into organic compounds emerged from these simulations are formulated.