Structural and Dynamical Differences in the Spike Protein RBD in the SARS-CoV-2 Variants B.1.1.7 and B.1.351
Structural and Dynamical Differences in the Spike Protein RBD in the SARS-CoV-2 Variants B.1.1.7 and B.1.351
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DOI：
10.1021/acs.jpcb.1c01626
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发表时间：
2021-06-10
影响因子：
3.3
通讯作者：
Chapagain, Prem P.
中科院分区：
文献类型：
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作者：
Bhattarai, Nisha;Baral, Prabin;Chapagain, Prem P.
2019年底开始的新型冠状病毒（SARS-CoV-2）大流行导致全球数亿病例和数百万人死亡。虽然有疫苗可用，但病毒正在变异形成新的毒株，其中包括表现出增强的传染性和传染性的变体B.1.1.7和B.1.351。在这项研究中，我们进行了分子动力学模拟，以探讨病毒刺突蛋白受体结合结构域（RBD）与宿主受体ACE 2的相互作用的突变的作用。我们发现，氢键网络重排的变体，也是新的氢键之间建立的RBD和ACE 2作为突变的结果。我们研究了三种变体：野生型（WT）、B.1.1.7和B.1.351。我们发现B.1.351变体（也称为501Y.V2）在涉及残基K484的RBD环片段中显示出更大的灵活性，而RBD-ACE 2复合物显示出更高的稳定性。允许更灵活的界面的突变可以产生更稳定的复合物，这可能是导致突变变体的感染性增加的因素。
The novel coronavirus (SARS-CoV-2) pandemic that started in late 2019 is responsible for hundreds of millions of cases worldwide and millions of fatalities. Though vaccines are available, the virus is mutating to form new strains among which are the variants B.1.1.7 and B.1.351 that demonstrate increased transmissivity and infectivity. In this study, we performed molecular dynamics simulations to explore the role of the mutations in the interaction of the virus spike protein receptor binding domain (RBD) with the host receptor ACE2. We find that the hydrogen bond networks are rearranged in the variants and also that new hydrogen bonds are established between the RBD and ACE2 as a result of mutations. We investigated three variants: the wild-type (WT), B.1.1.7, and B.1.351. We find that the B.1.351 variant (also known as 501Y.V2) shows larger flexibility in the RBD loop segment involving residue K484, yet the RBD-ACE2 complex shows higher stability. Mutations that allow a more flexible interface that can result in a more stable complex may be a factor contributing to the increased infectivity of the mutated variants.