Computational prediction of the effect of mutations in the receptor-binding domain on the interaction between SARS-CoV-2 and human ACE2

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ÇELİK İ., Khan A., Dwivany F. M., Fatimawali F., Wei D., Tallei T. E.

Molecular Diversity, vol.26, no.6, pp.3309-3324, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1007/s11030-022-10392-x
  • Journal Name: Molecular Diversity
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.3309-3324
  • Keywords: SARS-CoV-2, Receptor-binding domain, Spike, hACE, Mutation, In Silico, PROTEIN-PROTEIN, WEB SERVER, COMPENSATION, RECOGNITION, DOCKING, HDOCK
  • Kayseri University Affiliated: No


© 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 continues to mutate. Numerous studies have indicated that this viral mutation, particularly in the receptor-binding domain area, may increase the viral affinity for human angiotensin-converting enzyme 2 (hACE2), the receptor for viral entry into host cells, thereby increasing viral virulence and transmission. In this study, we investigated the binding affinity of SARS-CoV-2 variants (Delta plus, Iota, Kappa, Mu, Lambda, and C.1.2) on hACE2 using computational modeling with a protein–protein docking approach. The simulation results indicated that there were differences in the interactions between the RBD and hACE2, including hydrogen bonding, salt bridge interactions, non-bonded interactions, and binding free energy differences among these variants. Molecular dynamics simulations revealed that mutations in the RBD increase the stability of the hACE2-spike protein complex relative to the wild type, following the global stability trend and increasing the binding affinity. The value of binding-free energy calculated using molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) indicated that all mutations in the spike protein increased the contagiousness of SARS-CoV-2 variants. The findings of this study provide a foundation for developing effective interventions against these variants. Graphical abstract: [Figure not available: see fulltext.] Computational modeling elucidates that the spike protein of SARS-CoV-2 variants binds considerably stronger than the wild-type to hACE2.