Redefining Antibacterial Strategies with computational Screening of Benzimidazole Ligands Against VanZ Protein for Alternatives of Antibiotic.

Abstract

VanZ has crucial involvement in the modification of the bacterial peptidoglycan precursor and blocking its competence to bind with vancomycin and other related antibiotics. Hence targeting this protein can be an excellent option for combating the antibacterial resistance, particularly in the context of glycopeptide antibiotics like vancomycin. Hence, in this study, we have focused on the screening of 323 benzimidazole-based ligands for their possible interaction with the binding pocket of VanZ. The screening was based on the binding affinity values derived from molecular docking analysis. Furthermore, we had conducted an interacting amino acid analysis and we found six ligands that demand additional investigation. Consequently, we conducted molecular dynamics (MD) simulations using the optimal pose of VanZ to validate the stability of these VanZ–ligand complex and strengthen the consistency of the molecular docking results. Additionally, the pharmacological parameter was checked for all the six compounds. In summary, using the computational studies, we have successfully identified the putative candidates, which can be used for further in-vivo analyses. Our comprehensive approach can serve as a basis for the development of targeted compounds with enhanced efficacy against VanZ.