N501Y mutation in SARS-CoV-2 spike RBD protein enhances its binding to ACE2 receptor
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Abstract
Studies have indicated that the N501Y mutation in the spike protein of SARS-CoV-2 enhances the binding efficiency between its receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor, decreasing vaccine effectiveness and increasing the potential for viral infection. In this work, the structures of the wild-type RBD and N501Y-RBD in complex with the ACE2 receptor were generated to evaluate the effect of the N501Y mutation on their binding efficiency using molecular dynamics simulations, free energy calculations based on the MM/GB(PB)SA and SIE methods, and residue interaction network analysis. The results revealed that the N501Y-RBD/ACE2 complex displays higher compactness than the wild-type RBD/ACE2 structure via strong H-bonding, π–π, and van der Waals interactions. Moreover, the number of hot-spot residues in N501Y-RBD/ACE2 was higher than that of the wild-type RBD/ACE2 system. Structural and energetic insights gained from the study could be utilised for the design of novel drugs and vaccines against newly emerging coronavirus strains.
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