Deciphering the Protein Motion of S1 Subunit in SARS-CoV-2 Spike Glycoprotein Through Integrated Computational Methods
Abstract
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 Cα importance, we further suggested a relation between chains in the trimer spike protein, which may help in the vaccine design and antibody neutralization.