SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome

Maxwell I. Zimmerman, Justin R. Porter, Michael D. Ward, Sukrit Singh, Neha Vithani, Artur Meller, Upasana L. Mallimadugula, Catherine E. Kuhn, Jonathan H. Borowsky,  Rafal P. Wiewiora, Matthew F. D. Hurley, Aoife M Harbison, Carl A Fogarty, Joseph E. Coffland, Elisa Fadda, Vincent A. Voelz, John D. Chodera, Gregory R. Bowman.
Nature Chemistry 13:651, 2021. [DOI] [bioRxiv] [data] [FAH/MolSSI COVID-19 data sharing site]

To accelerate a multitude of drug development activities to combat the global threat posed by COVID-19, over a million citizen scientists have banded together through the Folding@home distributed computing project to create the world’s first Exascale computer and simulate protein dynamics. An unprecedented 0.1 seconds of simulation of the viral proteome reveal how the spike complex uses conformational masking to evade an immune response, conformational changes implicated in the function of other viral proteins, and cryptic pockets that are absent in experimental structures. These structures and mechanistic insights present new targets for the design of therapeutics..