Probing Mechanisms of Binding and Allostery in the SARS-CoV-2 Spike Omicron Variant Complexes with the Host Receptor: Revealing Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Communication with Allosteric Pockets.

ABSTRACT: In this study, we performed all-atom MD simulations of RBD-ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD-ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD-ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD-ACE2 complexes. By employing the ensemble-based global network analysis, we propose a community-based topological model of the O

SUBMITTER: Verkhivker G 

PROVIDER: S-EPMC9569682 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature