  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$\alpha$ importance, we further suggested a
relation between chains in the trimer spike protein, which may help in the
vaccine design and antibody neutralization.
