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Tuning Proton Transfer Thermodynamics in SARS-Cov-2 Main Protease: Implications for Catalysis and Inhibitor Design
preprintrevised on 11.01.2021, 08:39 and posted on 12.01.2021, 07:02 by Laura Zanetti-Polzi, Micholas Smith, Chris Chipot, James C. Gumbart, Diane L. Lynch, Anna Pavlova, Jeremy C. Smith, Isabella Daidone
In this computational work a hybrid quantum mechanics/molecular mechanics approach, the MD-PMM approach, is used to investigate the proton transfer reaction that activates the catalytic activity of SARS-CoV-2 main protease. The proton transfer thermodynamics is investigated for the apo ensyme (i.e., without any bound substrate or inhibitor) and in the presence of a inhibitor, N3, which was previously shown to covalently bind SARS-CoV-2 main protease.