Modelling SARS-CoV-2 spike-protein mutation effects on ACE2 binding.

ABSTRACT: The binding affinity of the SARS-CoV-2 spike (S)-protein to the human membrane protein ACE2 is critical for virus function. Computational structure-based screening of new S-protein mutations for ACE2 binding lends promise to rationalize virus function directly from protein structure and ideally aid early detection of potentially concerning variants. We used a computational protocol based on cryo-electron microscopy structures of the S-protein to estimate the change in ACE2-affinity due to S-protein mutation (ΔΔG_bind) in good trend agreement with experimental ACE2 affinities. We then expanded predictions to all possible S-protein mutations in 21 different S-protein-ACE2 complexes (400,000 ΔΔG_bind data points in total), using mutation group comparisons to reduce systema

SUBMITTER: Thakur S 

PROVIDER: S-EPMC9690204 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature