Identifying Inhibitor-SARS-CoV2-3CL^pro Binding Mechanism Through Molecular Docking, GaMD Simulations, Correlation Network Analysis and MM-GBSA Calculations.

ABSTRACT: The main protease of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as 3CL^pro, is crucial in the virus's life cycle and plays a pivotal role in COVID-19. Understanding how small molecules inhibit 3CL^pro's activity is vital for developing anti-COVID-19 therapeutics. To this end, we employed Gaussian accelerated molecular dynamics (GaMD) simulations to enhance the sampling of 3CL^pro conformations and conducted correlation network analysis (CNA) to explore the interactions between different structural domains. Our findings indicate that a CNA-identified node in domain II of 3CL^pro acts as a conduit, transferring conformational changes from the catalytic regions in domains I and II, triggered by the binding of inhibitors (7YY

SUBMITTER: Chen J 

PROVIDER: S-EPMC11857935 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature