Some recent SARS-CoV-2 variants appear to have increased transmissibility compared to the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on the target cells and infect them. In this study, we provide atomic-level insights into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities for the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than for the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.

中文翻译：

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对关键突变对 SARS-CoV-2 RBD-ACE2 结合影响的机制见解

与原始毒株相比，最近的一些 SARS-CoV-2 变种似乎具有更高的传染性。一个潜在的机制可能是变体结合靶细胞上的受体并感染它们的能力得到提高。在这项研究中，我们提供了对野生型 SARS-CoV-2 刺突蛋白的受体结合域 (RBD) 及其单 (N501Y)、双 (E484Q、L​​452R) 和三重 (N501Y) 结合的原子级见解。 、E484Q、L​​452R) 突变为人类 ACE2 受体的变体。使用广泛的全原子分子动力学模拟和高级自由能计算，我们估计了相关的结合亲和力和结合热点。我们观察到突变体 RBD 的显着二级结构变化，这导致不同的结合亲和力。我们发现双 (E484Q,