计算洞察 SARS-CoV-2 刺突蛋白的别构效应和动态结构特征。
Computational Insights into the Allosteric Effect and Dynamic Structural Features of the SARS-COV-2 Spike Protein.
机构信息
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, P. R. China.
College of Resources and Environment, University of the Chinese Academy of Sciences, Beijing, 100049, P. R. China.
出版信息
Chemistry. 2022 Jan 27;28(6):e202104215. doi: 10.1002/chem.202104215. Epub 2022 Jan 19.
COVID-19 caused by SARS-COV-2 is continuing to surge globally. The spike (S) protein is the key protein of SARS-COV-2 that recognizes and binds to the host target ACE2. In this study, molecular dynamics simulation was used to elucidate the allosteric effect of the S protein. Binding of ACE2 caused a centripetal movement of the receptor-binding domain of the S protein. The dihedral changes in Phe329 and Phe515 played a key role in this process. Two potential cleavage sites S1/S2 and S2' were exposed on the surface after the binding of ACE2. The binding affinity of SARS-COV-2 S protein and ACE2 was higher than that of SARS-COV. This was mainly due to the mutation of Asp480 in SARS-COV to Ser494 in SARS-COV-2, which greatly weakened the electrostatic repulsion. The result provides a theoretical basis for the SARS-COV-2 infection and aids the development of biosensors and detection reagents.
由 SARS-CoV-2 引起的 COVID-19 在全球范围内继续激增。刺突（S）蛋白是 SARS-CoV-2 的关键蛋白，它识别并结合宿主靶标 ACE2。在这项研究中，使用分子动力学模拟来阐明 S 蛋白的变构效应。ACE2 的结合导致 S 蛋白受体结合域的向心运动。二面角变化 Phe329 和 Phe515 在该过程中起关键作用。在与 ACE2 结合后，S1/S2 和 S2'两个潜在的切割位点暴露在表面上。SARS-CoV-2 S 蛋白和 ACE2 的结合亲和力高于 SARS-CoV。这主要是由于 SARS-CoV 中的 Asp480 突变为 SARS-CoV-2 中的 Ser494，大大减弱了静电排斥。该结果为 SARS-CoV-2 感染提供了理论依据，并有助于生物传感器和检测试剂的开发。
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