Computer Modeling of the Mechanisms of Enzymatic Reactions: Lessons from 20 Years of Practice

M. G. Khrenova^a^,^b^, *, T. I. Mulashkina^a^,^b, A. M. Kulakova^a^,^b, I. V. Polyakov^a^,^b, and A. V. Nemukhin^a^,^†

^aDepartment of Chemistry, Moscow State University, Moscow, 119991 Russia

^bEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334 Russia

Correspondence to: *e-mail: mkhrenova@lcc.chem.msu.ru

^†Deceased.

Received 30 October, 2023

Abstract— The combined quantum mechanics/molecular mechanics method is most often used to describe the molecular mechanisms of enzymatic reactions. The review discusses the main methodological issues, gives practical recommendations, and also illustrates the progress of the method over the past 20 years using an important example of the reaction of guanosine triphosphate hydrolysis by a protein complex.

Keywords: QM/MM, reaction mechanism, enzymatic catalysis, protein complex, molecular modeling

DOI: 10.3103/S0027131424700093