Molecular Dynamic Simulations of Folding and Dimerization in Mutations Found in the s2m Motif of SARS‐Cov‐2

Mackenstein, Nicole; Pellegrene, Kendy; Shine, Morgan; Lackey, Patrick; Mihailescu, Mihaela‐Rita; Evanseck, Jeffery

SARS‐CoV‐2, the virus responsible for the COVID‐19 pandemic, contains a highly conserved stem‐loop within the 3’ untranslated region called the s2m motif. Evidence suggests that the s2m motif plays a key role in replication and recombination of the virus. In SARS‐CoV‐2 we see slight differences in the s2m sequence from SARS‐CoV‐1, and the functional result of this mutation is unknown. We have also observed other mutations in the s2m motif commonly reported in COVID‐19 patients in positions previously thought to be invariant. To better understand dimerization in the s2m region we used molecular dynamics simulations to analyze the folding of the mutant as monomers. Using AmberTools and NAMD, systems for the sequences were created, minimized, equilibrated, and then submitted for production. The results were aligned to the SARS‐CoV‐2 reference sequence using VMD and analyzed to find changes in thermodynamics, positions of the bases, and RSMD between the reference sequence and the mutants.