Key Laboratory for Multiscale Simulation of Complex Systems, VNU University of Science, Vietnam National University, 334 Nguyen Trai street, Hanoi, 11416, Vietnam.
Faculty of Materials Science and Engineering, Phenikaa Institute for Advanced Study, Phenikaa University, Hanoi, 12116, Vietnam.
J Mol Model. 2022 Sep 8;28(10):305. doi: 10.1007/s00894-022-05231-7.
The pandemic of COVID-19 severe acute respiratory syndrome, which was fatal for millions of people worldwide, triggered the race to understand in detail the molecular mechanisms of this disease. In this work, the differences of interactions between the SARS-CoV/SARS-CoV-2 Receptor binding domain (RBD) and the human Angiotensin Converting Enzyme 2 (ACE2) receptor were studied using in silico tools. Our results show that SARS-CoV-2 RBD is more stable and forms more interactions with ACE2 than SARS-CoV. At its interface, three stable binding patterns are observed and named red-K31, green-K353 and blue-M82 according to the central ACE2 binding residue. In SARS-CoV instead, only the first two binding patches are persistently formed during the MD simulation. Our MM/GBSA calculations indicate the binding free energy difference of about 2.5 kcal/mol between SARS-CoV-2 and SARS-CoV which is compatible with the experiments. The binding free energy decomposition points out that SARS-CoV-2 RBD-ACE2 interactions of the red-K31 ([Formula: see text]) and blue-M82 ([Formula: see text]) patterns contribute more to the binding affinity than in SARS-CoV ([Formula: see text] for red-K31), while the contribution of the green-K353 pattern is very similar in the two strains ([Formula: see text] and [Formula: see text] for SARS-CoV-2 and SARS-CoV, respectively). Five groups of mutations draw our attention at the RBD-ACE2 binding interface, among them, the mutation -PPA469-471/GVEG482-485 has the most important and favorable impact on SARS-CoV-2 binding to the ACE2 receptor. These results, highlighting the molecular differences in the binding between the two viruses, contribute to the common knowledge about the new corona virus and to the development of appropriate antiviral treatments, addressing the necessity of ongoing pandemics.
COVID-19 严重急性呼吸综合征的大流行对全球数百万人来说是致命的，这促使人们竞相详细了解这种疾病的分子机制。在这项工作中，使用了计算机模拟工具研究了 SARS-CoV/SARS-CoV-2 受体结合域（RBD）与人类血管紧张素转换酶 2（ACE2）受体之间相互作用的差异。我们的结果表明，SARS-CoV-2 RBD 比 SARS-CoV 更稳定，与 ACE2 形成更多的相互作用。在其界面上，观察到三个稳定的结合模式，并根据 ACE2 的中心结合残基分别命名为红色-K31、绿色-K353 和蓝色-M82。在 SARS-CoV 中，只有前两个结合斑块在 MD 模拟过程中持续形成。我们的 MM/GBSA 计算表明，SARS-CoV-2 和 SARS-CoV 之间的结合自由能差异约为 2.5 kcal/mol，这与实验结果相符。结合自由能分解指出，SARS-CoV-2 RBD-ACE2 相互作用的红色-K31 ([Formula: see text]) 和蓝色-M82 ([Formula: see text]) 模式比 SARS-CoV 中的相互作用 ([Formula: see text] 对于红色-K31) 更有助于结合亲和力，而绿色-K353 模式的贡献在两种菌株中非常相似 ([Formula: see text] 和 [Formula: see text] 分别用于 SARS-CoV-2 和 SARS-CoV)。在 RBD-ACE2 结合界面上有五组突变引起了我们的注意，其中突变 -PPA469-471/GVEG482-485 对 SARS-CoV-2 与 ACE2 受体的结合具有最重要和最有利的影响。这些结果突出了两种病毒之间结合的分子差异，有助于增加对新型冠状病毒的共同认识，并为开发适当的抗病毒治疗方法做出贡献，以应对持续的大流行。
