The binding process of angiotensin-converting enzyme 2 (ACE2) to the receptor-binding domain (RBD) of the severe acute respiratory syndrome-like coronavirus 2 spike protein was investigated using molecular dynamics simulation and the three-dimensional reference interaction-site model theory. The results suggested that the protein-binding process consists of a protein–protein approaching step, followed by a local structural rearrangement step. In the approaching step, the interprotein interaction energy decreased as the proteins approached each other, whereas the solvation free energy increased. As the proteins approached, the glycan of ACE2 first established a hydrogen bond with the RBD. Thereafter, the number of interprotein hydrogen bonds increased rapidly. The solvation free energy increased because of the desolvation of the protein as it approached its partner. The spatial distribution function of the solvent revealed the presence of hydrogen bonds bridged by water molecules on the RBD–ACE2 interface. Finally, principal component analysis revealed that ACE2 showed a pronounced conformational change, whereas there was no significant change in RBD.

中文翻译：

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基于 MD 和 3D-RISM 理论的 SARS-CoV-2 RBD-ACE2 结合过程的计算分析

利用分子动力学模拟和三维参考相互作用位点模型理论研究了血管紧张素转换酶2（ACE2）与严重急性呼吸综合征样冠状病毒2刺突蛋白受体结合域（RBD）的结合过程。结果表明，蛋白质结合过程包括蛋白质-蛋白质接近步骤，随后是局部结构重排步骤。在接近步骤中，随着蛋白质彼此接近，蛋白质间相互作用能降低，而溶剂化自由能增加。当蛋白质接近时，ACE2 的聚糖首先与 RBD 建立氢键。此后，蛋白质间氢键的数量迅速增加。由于蛋白质在接近其伴侣时发生去溶剂化，因此溶剂化自由能增加。溶剂的空间分布函数揭示了 RBD-ACE2 界面上水分子桥接的氢键的存在。最后，主成分分析显示ACE2表现出明显的构象变化，而RBD则没有显着变化。