论文标题
通过集成的计算方法，在SARS-COV-2峰值糖蛋白中解解S1亚基的蛋白质运动
Deciphering the Protein Motion of S1 Subunit in SARS-CoV-2 Spike Glycoprotein Through Integrated Computational Methods
论文作者
论文摘要
新颖的严重急性呼吸综合症冠状病毒2（SARS-COV-2）是全球主要的公共卫生紧急情况，已感染了超过150万美元的人。峰值糖蛋白中S1亚基的部分开放状态被认为对宿主细胞的感染至关重要，并表示为中和抗体的关键靶标。但是，阐明从封闭状态到部分开放状态的过渡的机制仍然不清楚。在这里，我们应用了马尔可夫状态模型，过渡路径理论和随机森林的组合来分析S1运动。我们的结果探索了受体结合域的完全构象运动，从埋葬，部分开放到脱离状态。我们还在数字上确认了这些状态之间的过渡概率。基于动力学行为和主链C $α$重要性的不对称性，我们进一步提出了三聚峰蛋白中链之间的关系，这可能有助于疫苗设计和抗体中和。
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major worldwide public health emergency that has infected over $1.5$ million people. The partially open state of S1 subunit in spike glycoprotein is considered vital for its infection with host cell and is represented as a key target for neutralizing antibodies. However, the mechanism elucidating the transition from the closed state to the partially open state still remains unclear. Here, we applied a combination of Markov state model, transition path theory and random forest to analyze the S1 motion. Our results explored a promising complete conformational movement of receptor-binding domain, from buried, partially open, to detached states. We also numerically confirmed the transition probability between those states. Based on the asymmetry in both the dynamics behavior and backbone C$α$ importance, we further suggested a relation between chains in the trimer spike protein, which may help in the vaccine design and antibody neutralization.
