Exploring the Regulatory Function of the N-terminal Domain of SARS-CoV-2 Spike Protein Through Molecular Dynamics Simulation

Li, Yao; Wang, Tong; Zhang, Juanrong; Shao, Bin; Gong, Haipeng; Wang, Yusong; Liu, Siyuan; Liu, Tie-Yan

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. We performed molecular dynamics simulation on the S protein with a focus on the function of its N-terminal domains (NTDs). Our 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, we propose that the NTD-RBD interface should be a potential drug target.