Interaction of Sars-Cov-2 Delta Variant B.1.617.2 with Antibody Cr3022: Homology Modelling and Molecular Dynamics Studies

Abstract

In this study we modelled various possible spike protein (S1) structures for Delta SARS-CoV-2 (B.1.617.2) using homology modelling (SWISS-MODEL builder). The reliability of the structures is tested by means of global model quality estimation (GMQE), qualitative model energy analysis (QMEAN4) score and Ramachandran plots. We also tested the thermodynamic flexibility and highlight the impact of mutation at the receptor-binding domain (RBD) of B.1.617.2. It is found that all mutations increase the stability of proteins (ΔΔG) and decrease the entropies which cause the folding of protein structures. An exceptional case is noted for the mutation of G614D variant which indicates the dynamic movement of aspartic acid, D. For these mutations, vibration entropy change is found to be within the range of 0.133 kcal/mol/K - 0.004 kcal/mol/K. Temperature dependent free energy change values (ΔG) for Wild type is found to be -0.1 kcal/mol whereas all other cases exhibit values within the range of -5.1 to -5.5 kcal/mol. Mutation on spike increases the interaction with the glycoprotein antibody CR3022 and the binding affinity (CLUSpro energy = -99.7 kcal/mol). The stability of Delta variant with the antibody CR3022 is further confirmed by molecular dynamics (MD) simulations. Molecular docking study for the Delta variant with antibodies, such as, Etesevimab, Bebtelovimab, BD-368-2, Imdevimab, Bamlanivimab and Casirivimab, exhibit a substantially decreased docking score (-61.7 kcal/mol to -112.0 kcal/mol) and the disappearance of several hydrogen bond interactions. The current results indicate that antibody resistance increases significantly for delta as compared to Wild type which indicates that the marketed/launched vaccines will be less effective for Delta.

Keywords: Homology modelling, SARS-CoV-2, Delta, CR3022, molecular dynamics