Spike Protein Mutation-Induced Changes in the Kinetic and Thermodynamic Behavior of Its Receptor Binding Domains Explain Their Higher Propensity to Attain Open States in SARS-CoV-2 Variants of Concern.

ABSTRACT: Spike (S) protein opening in SARS-CoV-2 controls the accessibility of its receptor binding domains (RBDs) to host receptors and immune recognition. Along the evolution of SARS-CoV-2 to its variants of concern (VOC)-alpha, beta, gamma, delta, and omicron-their S proteins showed a higher propensity to attain open states. Deciphering how mutations in S protein can shape its conformational dynamics will contribute to the understanding of viral host tropism. Here using microsecond-scale multiple molecular dynamics simulations (MDS), we provide insights into the kinetic and thermodynamic contributions of these mutations to RBD opening pathways in S proteins of SARS-CoV-2 VOCs. Mutational effects were analyzed using atomistic (i) equilibrium MDS of closed and open states of S proteins and (ii) no

SUBMITTER: Singh J 

PROVIDER: S-EPMC10604015 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature