Ishikawa Takeshi, Ozono Hiroki, Akisawa Kazuki, Hatada Ryo, Okuwaki Koji, Mochizuki Yuji
Department of Chemistry, Biotechnology, and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima, Kagoshima 890-0065, Japan.
Department of Chemistry and Research Center for Smart Molecules, Faculty of Science, Rikkyo University, 3-34-1 Nishi-ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
J Phys Chem Lett. 2021 Nov 25;12(46):11267-11272. doi: 10.1021/acs.jpclett.1c02788. Epub 2021 Nov 12.
Visualization of the interfacial electrostatic complementarity (VIINEC) is a recently developed method for analyzing protein-protein interactions using electrostatic potential (ESP) calculated via the fragment molecular orbital method. In this Letter, the molecular interactions of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with human angiotensin-converting enzyme 2 (ACE2) and B38 neutralizing antibody were examined as an illustrative application of VIINEC. The results of VIINEC revealed that the E484 of RBD has a role in making a local electrostatic complementary with ACE2 at the protein-protein interface, while it causes a considerable repulsive electrostatic interaction. Furthermore, the calculated ESP map at the interface of the RBD/B38 complex was significantly different from that of the RBD/ACE2 complex, which is discussed herein in association with the mechanism of the specificity of the antibody binding to the target protein.
界面静电互补可视化（VIINEC）是一种最近开发的方法，用于使用通过片段分子轨道方法计算的静电势（ESP）分析蛋白质-蛋白质相互作用。在这篇快报中，作为VIINEC的一个示例性应用，研究了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白的受体结合域（RBD）与人血管紧张素转换酶2（ACE2）和B38中和抗体的分子相互作用。VIINEC的结果表明，RBD的E484在蛋白质-蛋白质界面处与ACE2形成局部静电互补方面发挥作用，同时它会引起相当大的排斥性静电相互作用。此外，RBD/B38复合物界面处计算得到的ESP图与RBD/ACE2复合物的ESP图有显著差异，本文结合抗体与靶蛋白结合特异性的机制对此进行了讨论。
