The SARS-CoV-2 virus is a strain of coronaviruses, named for the characteristic trimeric spike (S) glycoproteins that protrude from the viral membrane surface. The S proteins are type I fusion proteins, which upon recognition of ACE2, their host cell receptor, undergo substantial conformational change leading to membrane fusion and viral entry. Using molecular dynamics simulations, we have investigated several aspects for both the conformational landscape of the pre-fusion S protein as well as the receptor-binding process. Before binding, the receptor-binding domain on the S protein must first open to make the binding site accessible. We have carried out two-dimensional replica-exchange umbrella sampling to determine the minimum-free-energy pathway for this opening using NAMD on the nation’s largest supercomputer, Summit at Oak Ridge National Laboratory. Our simulations reveal, in particular, the role of S protein glycans in modulating the opening process. We also investigated the roles of a key stabilizing diproline mutation as well as of the now-dominant D614G variant.

Free-energy calculations of SARS-CoV-2 spike protein opening

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.