Effect on the conformations of the spike protein of SARS-CoV-2 due to mutation.

Abstract

The spike protein of SARS-CoV-2 mediates receptor binding and cell entry and is the key immunogenic target for virus neutralization and the present attention of many vaccine layouts. It exhibits significant conformational flexibility. We study the structural fluctuations of spike protein among the most common mutations that appeared in the variant of concerns (VOC). We report the thermodynamics of conformational changes in mutant spike protein with respect to the wild-type from the distributions of the dihedral angles obtained from the equilibrium configurations generated via all-atom molecular dynamics simulations. We find that the mutation causes the increase in distance between the N-terminal domain and receptor binding domain, leading to an obtuse angle cosine θ distribution in the trimeric structure in spike protein. Thus, an increase in open state is conferred to the more infectious variants of SARS-CoV-2. The thermodynamically destabilized and disordered residues of receptor binding motif among the mutant variants of spike protein are proposed to serve as better binding sites for the host factor. We identify a short stretch of region connecting the N-terminal domain and receptor binding domain forming a linker loop where many residues undergo stabilization in the open state compared to the closed one.