上位性
分子动力学
氢键
结合能
生物物理学
生物信息学
化学
相互作用能
受体
突变
结合位点
对接(动物)
分子
生物
计算化学
生物化学
物理
基因
医学
护理部
有机化学
核物理学
作者
Xu-Dong Hou,Jiali Gao,Yingjie Wang
标识
DOI:10.1021/acs.jpclett.2c02209
摘要
The hypermutated receptor binding domain (RBD) of the Omicron (B.1.1.529) lineage exhibits a different binding interface with human angiotensin-converting enzyme 2 (ACE2) relative to that of the wild-type Wuhan Hu-1, yet how the altered interaction will affect viral evolution is largely unknown. Here, we used molecular dynamics simulation to characterize the binding features of the Omicron BA.1/hACE2 complex and used free energy perturbation calculations to assess the ongoing and putative variations. The complex reveals a substantial rearrangement of the interfacial hydrogen-bond network: R493 of RBD forms a dynamic electrostatic interaction with both E35 and D38 of hACE2, which prohibits the hydrogen bonds of R498-D38 and Y449-D38. Whereas most circulating mutations minimally affect RBD binding to hACE2, the charge-altering mutation R493Q attenuates the affinity by abolishing the electrostatic interaction. However, the potential variants H505Y or N417K/R493Q could restore and gain even greater binding affinities than BA.1 as a result of their optimized interaction network and epistasis effects.
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