Computation of the Binding Energies between Human ACE2 and Spike RBDs of the Original Strain, Delta and Omicron Variants of the SARS‐CoV‐2: A DFT Simulation Approach

Abstract

The receptor binding domain (RBD) of SARS‐CoV‐2 binds to human ACE2 leading to infection. In this study, the complexes that are formed by the attachment of the SARS‐CoV‐2 spike RBDs of the original strain, delta and omicron variants to the human ACE2 are investigated via density functional theory (DFT) simulations to obtain binding energies. The DFT computations are performed without fragmenting the interfaces to involve longer‐range interactions for improved accuracy, which is one of the primary features of the approach used in this study. Basis set superposition error corrections and van der Waals dispersions are also included in the DFT simulations. The binding energies of the SARS‐CoV‐2 spike RBDs of the original strain, delta and omicron variants to the human ACE2 are computed as −4.76, −6.68, and −11.77 eV, respectively. These binding energy values indicate that the binding of the omicron variant to the ACE2 is much more favorable than the binding of the original strain and the delta variant, which constitute a molecular reason for the takeover of the omicron variant. The binding energies and the decomposition of these energies found in this study are expected to aid in the development of neutralizing agents.

Interaction of SARS-CoV-2 with host cells and antibodies: experiment and simulation

“…297 DFT simulations gave Δ G bind = −109.77, −154.04, and −271.42 kcal mol −1 for WT, Delta, and Omicron BA.1, respectively. 298 Although this result qualitatively agrees with other in silico and in vitro studies, the absolute binding free energy is are far from experimental data. In general, different Omicron sub-lineages have a slight difference in binding affinity to ACE2 299 indicating their similar ability to enter host cells.…”

The Impact of Mutation Sets in Receptor-Binding Domain of SARS-CoV-2 Variants on Stability of the RBD–ACE2 Complex

“…The binding affinity of the Omicron variant was characterized previously in several studies. For comparison in the study [ 63 ], complexes of ACE2 with the WT, Delta and Omicron variants were investigated via density functional theory (DFT) simulations to obtain binding energies. The results indicated that the binding of the Omicron variant to the ACE2 was much more favorable than the binding of the Delta variant and, especially, the WT of the virus.…”