Landscape-Based Mutational Sensitivity Cartography and Network Community Analysis of the SARS-CoV-2 Spike Protein Structures: Quantifying Functional Effects of the Circulating D614G Variant

We developed and applied a computational approach to simulate functional effects of the global circulating mutation D614G SARS-CoV-2 spike protein. All-atom molecular dynamics simulations are combined with deep mutational scanning analysis residue interaction networks investigate conformational landscapes energetics proteins in different states mutant. The results collective motions demonstrated that D614 site plays key regulatory role governing transitions between open closed states. Using sensitivity protein residues, we identified stability hotspots structures mutant trimers. suggest can induce increased form acting as driver changes, which may result exposure host receptor promote infectivity virus. network community showed enhance long-range couplings domains strengthen interdomain interactions form, supporting reduced shedding mechanism. This study provides landscape-based perspective atomistic view allosteric proteins, offering useful insight into mechanisms underpinning mutations.