Computational Insights into the Allosteric Effect and Dynamic Structural Features of the SARS‐COV‐2 Spike Protein

Abstract

COVID‐19 caused by SARS‐COV‐2 is continuing to surge globally. The spike (S) protein is the key protein of SARS‐COV‐2 that recognizes and binds to the host target ACE2. In this study, molecular dynamics simulation was used to elucidate the allosteric effect of the S protein. Binding of ACE2 caused a centripetal movement of the receptor‐binding domain of the S protein. The dihedral changes in Phe329 and Phe515 played a key role in this process. Two potential cleavage sites S1/S2 and S2′ were exposed on the surface after the binding of ACE2. The binding affinity of SARS‐COV‐2 S protein and ACE2 was higher than that of SARS‐COV. This was mainly due to the mutation of Asp480 in SARS‐COV to Ser494 in SARS‐COV‐2, which greatly weakened the electrostatic repulsion. The result provides a theoretical basis for the SARS‐COV‐2 infection and aids the development of biosensors and detection reagents.