Department of Biotechnology, Koneru Lakshmaiah Education Foundation (KLEF), Guntur, India.
Institute of Health and Sport, Victoria University, Melbourne, Australia.
J Biomol Struct Dyn. 2021 Jul;39(11):4015-4025. doi: 10.1080/07391102.2020.1773318. Epub 2020 Jun 4.
The novel corona virus disease 2019 (SARS-CoV 2) pandemic outbreak was alarming. The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE2) receptor initiates the entry of corona virus into the host cells leading to the infection. However, considering the mutations reported in the SARS-CoV 2 (nCoV), the structural changes and the binding interactions of the S-protein RBD of nCoV were not clear. The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. Based on the sequence alignment, a total of 58 residues were found mutated in nCoV S-protein RBD. These mutations led to the structural changes in the nCoV S-protein RBD 3d structure with 4 helices, 10 sheets and intermittent loops. The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD. Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE2 receptor with higher stability and rigidity. Concluding, the hotspots information will be useful in designing blockers for the nCoV spike protein RBD. [Formula: see text]Communicated by Ramaswamy H. Sarma.
新型冠状病毒病 2019（SARS-CoV-2）大流行疫情令人震惊。SARS-CoV（CoV）刺突蛋白（S-蛋白）受体结合域（RBD）与血管紧张素转化酶 2（ACE2）受体的结合启动了冠状病毒进入宿主细胞，导致感染。然而，考虑到报道的 SARS-CoV-2（nCoV）中的突变，nCoV S-蛋白 RBD 的结构变化和结合相互作用尚不清楚。本研究旨在通过计算方法阐明 nCoV S-蛋白 RBD 与 ACE2 受体之间的结构变化、热点结合残基及其相互作用。基于序列比对，共发现 nCoV S-蛋白 RBD 中有 58 个残基发生突变。这些突变导致 nCoV S-蛋白 RBD 3d 结构的结构变化，该结构有 4 个螺旋、10 个片层和间歇性环。nCoV RBD 被发现与 ACE2 受体结合有 11 个氢键和 1 个盐桥。通过模拟后相互作用分析确定的结合中的主要热点氨基酸包括 ACE2 受体中的 Glu35、Tyr83、Asp38、Lys31、Glu37 和 His34 氨基酸残基，以及 nCoV S-蛋白 RBD 中的 Gln493、Gln498、Asn487、Tyr505 和 Lys417 氨基酸残基。基于氢键、RMSD 和 RMSF、总能量和势能，nCoV 与 ACE2 受体的结合更稳定和刚性。总之，热点信息将有助于设计针对 nCoV 刺突蛋白 RBD 的阻断剂。[公式：见文本]由 Ramaswamy H. Sarma 传达。
