The COVID-19 pandemic sparked an unprecedented race in biotechnology in a search for effective therapies and a preventive vaccine. The continued appearance of SARS-CoV-2 variants of concern (VoCs) further swept the world. The entry of SARS-CoV-2 into cells is mediated by binding the receptor-binding domain (RBD) of the S protein to the cell-surface receptor, human angiotensin-converting enzyme 2 (hACE2). In this study, using a coarse-grained force field to parameterize the system, we employed steered-molecular dynamics (SMD) simulations to reveal the binding of SARS-CoV-2 Delta/Omicron RBD to hACE2. Our benchmarked results demonstrate a good correlation between computed rupture force and experimental binding free energy for known protein-protein systems. Moreover, our findings show that the Omicron RBD has a weaker binding affinity to hACE2, consistent with the respective experimental results. This indicates that our method can effectively be applied to other emerging SARS-CoV-2 strains.Communicated by Ramaswamy H. Sarma.
Keywords: RBD; coarse-grained model; hACE2; steered-molecular dynamics.