Testing Affordable Strategies for the Computational Study of Reactivity in Cysteine Proteases: The Case of SARS-CoV-2 3CL Protease Inhibition.

ABSTRACT: Cysteine proteases are an important target for the development of inhibitors that could be used as drugs to regulate the activity of these kinds of enzymes involved in many diseases, including COVID-19. For this reason, it is important to have methodological tools that allow a detailed study of their activity and inhibition, combining computational efficiency and accuracy. We here explore the performance of different quantum mechanics/molecular mechanics methods to explore the inhibition reaction mechanism of the SARS-CoV-2 3CL protease with a hydroxymethyl ketone derivative. We selected two density functional theory (DFT) functionals (B3LYP and M06-2X), two semiempirical Hamiltonians (AM1d and PM6), and two tight-binding DFT methods (DFTB3 and GFN2-xTB) to explore the free energy landscap

SUBMITTER: Ramos-Guzman CA 

PROVIDER: S-EPMC9115880 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature