Electrostatic Interactions Contribute to the Overall Structural Stability in Small Interfaces of Corona Viral Spike Glycoproteins

Abstract

The coronavirus outbreak and its mutant variants have harmed the health of the human populace and imperiled the world economy. Several studies are initiated across the globe using clinical biomarkers from hematological, immunological, and biochemical experiments. In addition, analysis of protein interfaces provides an understanding of the functioning of the coronavirus target proteins. This study examines the interfaces of spike glycoproteins in terms of large (vdW dominant) and small (vdW subdominant) interfaces. We also calculated Gibbs free energy (ΔG), residue propensity and hot-spot prediction for these interfaces. Dataset consisting of 115 (large interface with vdW dominant) and 18 (small interface with vdW subdominant) were obtained from PDB. Results show that 86% of the total interfaces were vdW dominant, while the rest, 14%, were sub-dominant in vdW energy. Interestingly, on average, we found the Gibbs free energy (ΔG) of large and small interfaces to be -21 and -30 kcal/mol respectively. We also found the interfaces of large and small to be highly pronounced with polar residues followed by hydrophobic residues in case of large interfaces and charged residues in case of small interfaces. We found and report methionine residues to be absent at the small interfaces having subdominant vdW energy. We also observed the majority of the interfaces to be rich in hotspot residues. Thus, the information on heteromeric interactions of glycoproteins may help develop new and productive therapeutic drugs.