Li Jiacheng, Ma Xiaoliang, Guo Shuai, Hou Chengyu, Shi Liping, Zhang Hongchi, Zheng Bing, Liao Chenchen, Yang Lin, Ye Lin, He Xiaodong
National Key Laboratory of Science and Technology on Advanced Composites in Special Environments Center for Composite Materials and Structures Harbin Institute of Technology Harbin 150080 P. R. China.
School of Electronics and Information Engineering Harbin Institute of Technology Harbin 150080 P. R. China.
Glob Chall. 2020 Oct 15;4(12):2000067. doi: 10.1002/gch2.202000067. eCollection 2020 Dec.
A recent experimental study found that the binding affinity between the cellular receptor human angiotensin-converting enzyme 2 (ACE2) and receptor-binding domain (RBD) in the spike (S) protein of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more than tenfold higher than that of the original severe acute respiratory syndrome coronavirus (SARS-CoV). However, main chain structures of the SARS-CoV-2 RBD are almost the same with that of the SARS-CoV RBD. Understanding the physical mechanism responsible for the outstanding affinity between the SARS-CoV-2 S and ACE2 is an "urgent challenge" for developing blockers, vaccines, and therapeutic antibodies against the coronavirus disease 2019 (COVID-19) pandemic. Taking into account the mechanisms of hydrophobic interaction, hydration shell, surface tension, and the shielding effect of water molecules, this study reveals a hydrophobic-interaction-based mechanism by means of which SARS-CoV-2 S and ACE2 bind together in an aqueous environment. The hydrophobic interaction between the SARS-CoV-2 S and ACE2 protein is found to be significantly greater than that between SARS-CoV S and ACE2. At the docking site, the hydrophobic portions of the hydrophilic side chains of SARS-CoV-2 S are found to be involved in the hydrophobic interaction between SARS-CoV-2 S and ACE2.
最近的一项实验研究发现，新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）蛋白中的细胞受体人血管紧张素转换酶2（ACE2）与受体结合域（RBD）之间的结合亲和力比原始严重急性呼吸综合征冠状病毒（SARS-CoV）高出十倍以上。然而，SARS-CoV-2 RBD的主链结构与SARS-CoV RBD几乎相同。了解SARS-CoV-2 S与ACE2之间出色亲和力的物理机制是开发针对2019冠状病毒病（COVID-19）大流行的阻滞剂、疫苗和治疗性抗体的“紧迫挑战”。考虑到疏水相互作用、水合壳、表面张力和水分子屏蔽效应的机制，本研究揭示了一种基于疏水相互作用的机制，通过该机制SARS-CoV-2 S和ACE2在水环境中结合在一起。研究发现，SARS-CoV-2 S与ACE2蛋白之间的疏水相互作用明显大于SARS-CoV S与ACE2之间的疏水相互作用。在对接位点，发现SARS-CoV-2 S亲水性侧链的疏水部分参与了SARS-CoV-2 S与ACE2之间的疏水相互作用。
