Toward atomistic models of intact severe acute respiratory syndrome coronavirus 2 via Martini coarse‐grained molecular dynamics simulations

The causative pathogen of coronavirus disease 2019 (COVID‐19), severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is an enveloped virus assembled by a lipid envelope and multiple structural proteins. In this study, by integrating experimental data, structural modeling, as well as coarse‐grained and all‐atom molecular dynamics simulations, we constructed multiscale models of SARS‐CoV‐2. Our 500‐ns coarse‐grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane‐embedded proteins and the surrounding lipid molecules in situ. Our results indicated that the membrane‐embedded proteins are highly dynamic, and certain types of lipids exhibit various binding preferences to specific sites of the membrane‐embedded proteins. The equilibrated virion model was transformed into atomic resolution, which provided a 3D structure for scientific demonstration and can serve as a framework for future exascale all‐atom molecular dynamics (MD) simulations. A short all‐atom molecular dynamics simulation of 255 ps was conducted as a preliminary test for large‐scale simulations of this complex system.