Spike proteins exist on the surface of SARS-CoV-2 and triggers the virus entry into a host cell. Conformational flexibility of the spike protein is essential when it recognizes the ACE2 receptor on the host cell surface in the virus entry. Therefore, conformational dynamics of the spike protein have been one of the central issues in structural and computational biology related to SARS-CoV-2. We have carried out conventional molecular dynamics (cMD) simulations, target MD (tMD), and MD simulations based on the generalized Replica Exchange with Solute Tempering (gREST) method of the protein using GENESIS software optimized to Fugaku supercomputer. In cMD simulations starting from inactive “down” and active “1_up” conformations, different glycans in spike protein play important roles on the stabilization. tMD is useful to connect the two structures and confirm the role of glycans observed in cMD simulations. However, these two methods have limitations in a conformational sampling of the protein, while gREST MD simulations allow us to explore a wider conformational space. Based on the free-energy landscapes from gREST simulations, we propose conformational pathways between “down” and “1_up” as well as “1_up” and “2_up” conformations, elucidating the role of glycans in the conformational changes. These results would be useful for rational designs of anti-virus drugs and vaccines in future.

Conformational flexibility and stability of SARS-CoV-2 spike protein in solution

ACS Spring Meeting 2021

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