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.

中文翻译：

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通过分子动力学模拟探索 SARS-CoV-2 刺突蛋白 N 端结构域的调节功能

SARS-CoV-2 是导致 COVID-19 大流行的原因。早期病毒感染由 SARS-CoV-2 同源三聚刺突 (S) 蛋白介导，其受体结合域 (RBD) 处于受体可接近状态。对 S 蛋白进行分子动力学模拟，重点关注其N端结构域 (NTD) 的功能。研究揭示NTD作为“楔子”，在S蛋白构象变化中发挥着至关重要的调节作用。仅当相邻的 NTD 通常会阻止 RBD 的运动（如楔子分离和摆动）时，才允许完整的 RBD 结构转变。基于这种 NTD“楔形”模型，提出 NTD-RBD 界面应该是潜在的药物靶点。