Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations.

ABSTRACT: The recent outbreak of novel "coronavirus disease 2019" (COVID-19) has spread rapidly worldwide, causing a global pandemic. In the present work, we have elucidated the mechanism of binding of two inhibitors, namely α-ketoamide and Z31792168, to SARS-CoV-2 main protease (M^pro or 3CL^pro) by using all-atom molecular dynamics simulations and free energy calculations. We calculated the total binding free energy (ΔG_bind) of both inhibitors and further decomposed ΔG_bind into various forces governing the complex formation using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Our calculations reveal that α-ketoamide is more potent (ΔG_bind= - 9.05 kcal/mol) compared to Z31792168 (ΔG_bind= - 3.25 kcal/mol) again

SUBMITTER: Sk MF 

PROVIDER: S-EPMC7284146 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature