Identifying promising druggable binding sites and their flexibility to target the receptor-binding domain of SARS-CoV-2 spike protein.

ABSTRACT: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for viral infection. The interaction of its receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2) protein is required for the virus to enter the host cell. We identified RBD binding sites to block its function with inhibitors by combining the protein structural flexibility with machine learning analysis. Molecular dynamics simulations were performed on unbound or ACE2-bound RBD conformations. Pockets estimation, tracking and druggability prediction were performed on a large sample of simulated RBD conformations. Recurrent druggable binding sites and their key residues were identified by clustering pockets based on their residue similarity. This protocol successfully id

SUBMITTER: Ghoula M 

PROVIDER: S-EPMC10023212 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature