Li Yao, Wang Tong, Zhang Juanrong, Shao Bin, Gong Haipeng, Wang Yusong, He Xinheng, Liu Siyuan, Liu Tie-Yan
MOE Key Laboratory of Bioinformatics School of Life Sciences Tsinghua University Beijing 100084 China.
Beijing Advanced Innovation Center for Structural Biology Tsinghua University Beijing 100084 China.
Adv Theory Simul. 2021 Oct;4(10):2100152. doi: 10.1002/adts.202100152. Epub 2021 Sep 2.
SARS-CoV-2 is what has caused the COVID-19 pandemic. Early viral infection is mediated by the SARS-CoV-2 homo-trimeric Spike (S) protein with its receptor binding domains (RBDs) in the receptor-accessible state. Molecular dynamics simulation on the S protein with a focus on the function of its -terminal domains (NTDs) is performed. The study reveals that the NTD acts as a "wedge" and plays a crucial regulatory role in the conformational changes of the S protein. The complete RBD structural transition is allowed only when the neighboring NTD that typically prohibits the RBD's movements as a wedge detaches and swings away. Based on this NTD "wedge" model, it is proposed that the NTD-RBD interface should be a potential drug target.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是导致2019冠状病毒病（COVID-19）大流行的病原体。早期病毒感染是由处于受体可及状态的SARS-CoV-2同三聚体刺突（S）蛋白及其受体结合域（RBD）介导的。针对S蛋白进行了分子动力学模拟，重点关注其N端结构域（NTD）的功能。研究表明，NTD充当“楔子”，在S蛋白的构象变化中起关键调节作用。只有当通常作为楔子阻止RBD移动的相邻NTD分离并摆动开时，完整的RBD结构转变才会发生。基于这种NTD“楔子”模型，有人提出NTD-RBD界面应是一个潜在的药物靶点。
