Omicron BA.1 and BA.2 variants increase the interactions of SARS-CoV-2 with ACE2

Golcuk M., Yildiz A., Gür M.

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, vol.117, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 117
  • Publication Date: 2022
  • Doi Number: 10.1016/j.jmgm.2022.108286
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, Computer & Applied Sciences, EMBASE, INSPEC, MEDLINE
  • Keywords: ACE2 receptor, MMPBSA, Molecular dynamics simulations, Omicron variant, SARS-CoV-2, Spike glycoprotein, BINDING
  • Istanbul Technical University Affiliated: Yes


SARS-CoV-2 infection is initiated by binding of the receptor-binding domain (RBD) of its spike glycoprotein to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptors in host cells. Recently detected Omicron variant of SARS-CoV-2 (B.1.1.529) is heavily mutated on RBD. First the BA.1 and later the BA.2 variant became the most dominant strains of the Omicron variant. To investigate how the mutations of these strains affect RBD-PD interactions, we performed all-atom molecular dynamics simulations of the BA.1 and BA.2 RBD-PD in the presence of full-length glycans, explicit water, and ions. Simulations revealed that RBDs of BA.1 and BA.2 variants exhibit a more dispersed interaction network and make an increased number of salt bridges and hydrophobic interactions with PD compared to wild-type RBD. Although BA.1 and BA.2 differ in two residues at the RBD-ACE2 interface, no major difference in RBD-PD interactions and binding strengths were observed be-tween these variants. Using the conformations sampled in each trajectory, the Molecular Mechanics Poisson -Boltzmann Surface Area (MMPBSA) method estimated-34% and-51% stronger binding free energies to PD for BA.1 and BA.2 RBD, respectively, than wild-type RBD, which may result in higher binding efficiency of the Omicron variant to infect host cells.