Entropic Overcompensation of the N501Y Mutation on SARS-CoV-2 S Binding to ACE2.

ABSTRACT: Recent experimental work has shown that the N501Y mutation in the SARS-CoV-2 S glycoprotein's receptor binding domain (RBD) increases binding affinity to the angiotensin-converting enzyme 2 (ACE2), primarily by overcompensating for a less favorable enthalpy of binding by greatly reducing the entropic penalty for complex formation, but the basis for this entropic overcompensation is not clear [Prévost et al. J. Biol. Chem.2021, 297, 101151]. We use all-atom molecular dynamics simulations and free-energy calculations to qualitatively assess the impact of the N501Y mutation on the enthalpy and entropy of binding of RBD to ACE2. Our calculations correctly predict that N501Y causes a less favorable enthalpy of binding to ACE2 relative to the original strain. Furthermore, we show that thi

SUBMITTER: Vergara NG 

PROVIDER: S-EPMC9843633 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature