Dynamic Interactions of Fully Glycosylated SARS-CoV-2 Spike Protein with Various Antibodies

Cao, Yiwei; Choi, Yeol Kyo; Frank, Martin; Woo, Hyeonuk; Park, Sang-Jun; Yeom, Min Sun; Seok, Chaok; Im, Wonpil

[Image: see text] The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a public health crisis, and the vaccines that can induce highly potent neutralizing antibodies are essential for ending the pandemic. The spike (S) protein on the viral envelope mediates human angiotensin-converting enzyme 2 binding and thus is the target of a variety of neutralizing antibodies. In this work, we built various S trimer–antibody complex structures on the basis of the fully glycosylated S protein models described in our previous work and performed all-atom molecular dynamics simulations to gain insight into the structural dynamics and interactions between S protein and antibodies. Investigation of the residues critical for S–antibody binding allows us to predict the potential influence of mutations in SARS-CoV-2 variants. Comparison of the glycan conformations between S-only and S–antibody systems reveals the roles of glycans in S–antibody binding. In addition, we explored the antibody binding modes and the influences of antibody on the motion of S protein receptor binding domains. Overall, our analyses provide a better understanding of S–antibody interactions, and the simulation-based S–antibody interaction maps could be used to predict the influences of S mutation on S–antibody interactions, which will be useful for the development of vaccine and antibody-based therapy.