Structure elucidation and computational studies of the thiazole derivative against SARS-CoV-2 virus: Insights from XRD, DFT, molecular docking, and molecular dynamics simulation

Abstract

• Structural investigation of thiazole derivative using crystal X-ray diffraction technique . • C-H...O intermolecular interactions are studied. • HOMO-LUMO and MEP analysis helped to understand the physical properties of the molecule. • The nature of non-covalent bonding characteristics were revealed by the NCI analysis. • Further, in silico studies like molecular docking and molecular dynamics simulation were performed. The present work is focused on the crystal structure, Hirshfeld surface, Density Functional Theory (DFT) studies of thiazole derivative N-benzyl-4-(4-bromophenyl)thaiazole-2-carboxamide ( TT4) . The crystal structure has been determined using single crystal X-ray diffraction analysis, which shows that the compound crystallizes in the monoclinic crystal system with space group P 2 1 / c. C-H⋯O type of hydrogen bond interaction is responsible for the crystal packing in crystal The molecular geometry optimization was performed by DFT calculations. The 2D scattered plot was generated by Reduced Density Gradient (RDG) analysis, which divulge the weak and noncovalent interactions in the compound TT4 . In silico studies were carried out to delve into the binding pattern of the TT4 compound against SARS-CoV-2 proteins using molecular docking and molecular dynamics simulation. Finally, the binding free energy and the contributed energies were derived using MM-GBSA approach. The 7K40-ligand complex showed the highest binding free energy, and among all other interactions, the contributions of the covalent binding and van der Waals energy were found to be significant.