Enhanced binding of the N501Y-mutated SARS-CoV-2 spike protein to the human ACE2 receptor: insights from molecular dynamics simulations

FEBS Letters

article

Binquan Luan¹  Haoran Wang²  Tien Huynh¹ 

[1] Computational Biological Center, IBM Thomas J. Watson Research;Neoland Biosciences

关键词: ACE2;    antibody;    N501Y;    SARS-CoV-2;    spike protein;   

DOI  :  10.1002/1873-3468.14076

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (B.1.1.7 and B.1351) have emerged harbouring mutations that make them highly contagious. The N501Y mutation within the receptor-binding domain (RBD) of the spike protein of these SARS-CoV-2 variants may enhance binding to the human angiotensin-converting enzyme 2 (hACE2). However, no molecular explanation for such an enhanced affinity has so far been provided. Here, using all-atom molecular dynamics simulations, we show that Y501 in the mutated RBD can be well-coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, which may increase the overall binding affinity of the RBD for hACE2 by approximately 0.81 kcal·mol −1 . The binding dynamics revealed in our study may provide a working model to facilitate the design of more effective antibodies.

【 授权许可】

Unknown