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

Igor V. Polyakov; Tatiana M. Domratcheva; Anna M. Kulakova; Alexander V. Nemukhin; Bella L. Grigorenko

doi:10.14529/jsfi220204

Authors

Igor V. Polyakov Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0001-5459-6709
Tatiana M. Domratcheva Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0002-7001-1114
Anna M. Kulakova Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0002-9732-0996
Alexander V. Nemukhin Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0002-4992-6029
Bella L. Grigorenko Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation https://orcid.org/0000-0003-1372-4692

DOI:

https://doi.org/10.14529/jsfi220204

Keywords:

computational modeling, molecular dynamics, quantum mechanics/molecular mechanics, protein-oxygen interaction, flavin-dependent enzymes

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.

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