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.