Departament d'Enginyeria Química, EEBE, Universitat Politècnica de Catalunya, C/ Eduard Maristany, 10-14, Ed. I2, 08019, Barcelona, Spain; Barcelona Research Center in Multiscale Science and Engineering, Universitat Politècnica de Catalunya, C/ Eduard Maristany, 10-14, 08019, Barcelona, Spain.
Departament d'Enginyeria Química, EEBE, Universitat Politècnica de Catalunya, C/ Eduard Maristany, 10-14, Ed. I2, 08019, Barcelona, Spain.
Biochimie. 2022 Feb;193:90-102. doi: 10.1016/j.biochi.2021.10.013. Epub 2021 Oct 25.
Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 μs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.
接种 SARS-CoV-2 疫苗在大多数国家刚刚开始。然而，针对 SARS-CoV-2 的特异性疫苗的开发并不是控制该病毒的唯一方法，单克隆抗体（mAbs）开始作为治疗 COVID-19 疾病的一种治疗选择而受到特别关注。在这里，我们研究了刺突糖蛋白（S 蛋白）的受体结合域（RBD）与两种 mAbs（CR3022 和 S309）和 ACE2 细胞受体之间的主要构象和相互作用，这两种 mAbs 作为 S 蛋白 RBD 上三个不同表位的主要代表。我们采用了 1 μs 加速分子动力学（aMD）和从头算混合分子动力学的组合方法，以确定在生理条件下最主要的相互作用。结果确定了最主要的受体结合图谱，氢键网络和在抗原-抗体界面构象中带电荷的原子之间的盐桥。对涉及 mAbs 和 ACE2 受体与 SARS-CoV-2 刺突糖蛋白的蛋白-蛋白相互作用的深入了解，增加了背景知识，有助于加快新疫苗和治疗药物的开发。
