SARS-COV-2 M^pro conformational changes induced by covalently bound ligands.

ABSTRACT: SARS-CoV-2's main protease (M^pro) interaction with ligands has been explored with a myriad of crystal structures, most of the monomers. Nonetheless, M^pro is known to be active as a dimer but the relevance of the dimerization in the ligand-induced conformational changes has not been fully elucidated. We systematically simulated different M^pro-ligand complexes aiming to study their conformational changes and interactions, through molecular dynamics (MD). We focused on covalently bound ligands (N1 and N3, ∼9 μs per system both monomers and dimers) and compared these trajectories against the apostructure. Our results suggest that the monomeric simulations led to an unrealistically flexible active site. In contrast, the M^pro dimer displayed a stable o

SUBMITTER: Ferreira GM 

PROVIDER: S-EPMC8442757 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature