Department of Chemistry, University of Southern California, 418 SGM Building, 3620 McClintock Avenue, Los Angeles, California 90089-1062, United States.
J Phys Chem B. 2020 Jul 16;124(28):5907-5912. doi: 10.1021/acs.jpcb.0c04317. Epub 2020 Jul 6.
The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.
由 SARS-CoV-2 引起的 COVID-19 已在全球范围内传播，并造成了巨大的生命和财产损失，因此迫切需要了解其传播过程，并寻找减缓疫情的方法。在这项工作中，我们使用粗粒化模型来计算 SARS-CoV-2 或 SARS-CoV 与其人类受体 ACE2 的结合自由能。对相互作用残基的自由能贡献的研究表明，位于受体结合域之外的残基是新型病毒更强结合的来源。因此，目前的结果表明，SARS-CoV-2 的关键进化发生在刺突蛋白三聚体的结合域之外。这种进化可能有助于病毒与 ACE2 结合后发生的构象变化和感染过程。通过研究 SARS-CoV 抗体 m396 与 SARS-CoV-2 之间的结合模式，发现缺失了远程能量贡献，这可能解释了此类抗体缺乏交叉反应性的原因。
