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

Abstract

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 N-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.

• Authors: Yao Li, Tong Wang, Juanrong Zhang, Bin Shao, Haipeng Gong, Yusong Wang, Xinheng He, Siyuan Liu, Tie-Yan Liu
• Journal: Advanced theory and simulations (Adv Theory Simul) Vol. 4 Issue 10 Pg. 2100152 (Oct 2021) ISSN: 2513-0390 [Electronic] Germany
• PMID: 34901736 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley‐VCH GmbH.