ABSTRACT
Recently detected Omicron variant of SARS-CoV-2 (B.1.1.529) is heavily mutated on the receptor-binding domain (RBDOmicron) of its spike glycoprotein (S). RBD plays a critical role in viral infection by binding to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptors in host cells. To investigate how Omicron mutations affect RBD-PD interactions, we performed all-atom molecular dynamics simulations of the RBDOmicron-PD in the presence of explicit water and ions. Simulations revealed that RBDOmicron exhibits a more dispersed interaction network on both sides of the RBD-PD interaction surface. Mutations resulted in an increased number of salt bridges and hydrophobic interactions between RBDOmicron and PD compared to wild-type RBD (RBDWT). Using the conformations sampled in each trajectory, the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method estimated ~44% stronger binding free energy for RBDOmicron compared to RBDWT, which may result in higher binding efficiency of the SARS-CoV-2 virus to infect host cells.
Competing Interest Statement
The authors have declared no competing interest.