Intermolecular Interaction Analyses on SARS-CoV-2 Receptor Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor-Blocking Antibody/peptide Using Fragment Molecular Orbital Calculation
Intermolecular Interaction Analyses on SARS-CoV-2 Receptor Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor-Blocking Antibody/peptide Using Fragment Molecular Orbital Calculation
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DOI：
10.26434/chemrxiv.14135138.v1
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
K. Watanabe;C. Watanabe;T. Honma;Y. Tian;Y. Kawashima;N. Kawashita;T. Takagi;Kaori Fukuzawa
中科院分区：
文献类型：
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作者：
K. Watanabe;C. Watanabe;T. Honma;Y. Tian;Y. Kawashima;N. Kawashita;T. Takagi;Kaori Fukuzawa
刺突糖蛋白（S蛋白）通过与人血管紧张素转换酶2（hACE 2）的分子间相互作用介导SARS-CoV-2进入。S蛋白的受体结合结构域（RBD）被认为是这种相互作用的关键，并作为许多中和抗体和抗病毒肽的靶标。本研究利用片段分子轨道（FMO）方法分析了RBD与抗体/多肽的相互作用，并提取了可用于表位的关键残基。RBD和12种抗体/肽之间的相互作用（以片段间相互作用能（IFIE）值评估）显示与实验活性pIC 50（R2 = 0.540）具有相当好的相关性。9个残基（T415、K417、Y 421、F456、A475、F486、N487、N501和Y505）被确认为关键残基。对相互作用能量分解分析（PIEDA）表明，氢键，静电相互作用和π轨道相互作用是重要的。我们的研究结果为理解SARS-CoV-2-抗体/肽结合提供了必要的信息，并可能在未来的抗体/抗病毒药物设计中发挥作用。
The spike glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction with human angiotensin-converting enzyme 2 (hACE2). The receptor-binding domain (RBD) of the S-protein has been considered critical for this interaction and acts as the target of numerous neutralizing antibodies and antiviral peptides. This study used the fragment molecular orbital (FMO) method to analyze the interactions between RBD and antibodies/peptides and extracted crucial residues that can be used to epitopes. The interactions evaluated as inter-fragment interaction energy (IFIE) values between the RBD and 12 antibodies/peptides showed a fairly good correlation with the experimental activity pIC50 (R2 = 0.540). Nine residues (T415, K417, Y421, F456, A475, F486, N487, N501, and Y505) were confirmed as crucial. Pair interaction energy decomposition analyses (PIEDA) showed that hydrogen bonds, electrostatic interactions, and π-orbital interactions are important. Our results provide essential information for understanding SARS-CoV-2-antibodies/peptide binding and may play roles in future antibody/antiviral drug design.