Intrinsic dynamics of SARS-CoV-2 spike proteins and structural changes using Principal Component and Anisotropic Network Model analysis

Several studies have revealed different conformations of SARS-CoV-2, which may obscure the study of significant structures. We have focused on the SARS-CoV-2 herringbone structure. 84 structures determined for these enzymes in the presence of various inhibitors, such as antibodies, nanostructures, and in unbound form allowed us to theorize a comprehensive comparative analysis of the conformational space accessed after ligand binding and its relationship to the intrinsic dynamics prior to ligand binding, as predicted by elastic lattice model analysis. We detailed the important zones of ligand coupling in the affinity energy measurements. Also, performed a detailed analysis of the SARS-CoV-2 spike protein's experimentally observed conformational changes upon binding to a variety of ligands, as well as those predicted by simple physics-based models based on the contact topology of its native fold. In both cases, the first major mode of structural change, PC1, observed in the experiments shows a correlation of 0.71 with a higher rank mode (ANM1-ANM2) intrinsically preferred by the unbound protein. The findings imply that basic but robust rules encoded in the protein structure play a prominent role in predefining ligand binding pathways, which could be useful in inhibitor development.