ABSTRACT
Drug discovery is an intensive and costly process, and computational approaches such as molecular docking can significantly accelerate the identification of promising lead molecules. In this study, molecular docking investigations were performed on previously synthesized camphor hydrazide (MBL-101 to MBL-106) and Isatin-based (MMP-01 to MMP-12) derivatives against ATP-dependent DNA ligase from bacteriophage (PDB ID: 1a0i) using Molegro Virtual Docker (MVD). The native ATP ligand exhibited the strongest binding affinity, with a MolDock score of –190.482 kcal/mol and a re-rank score of –114.713 kcal/mol. Among the synthesized ligands, MBL-103 (–116.521 kcal/mol) and MBL-106 (–112.338 kcal/mol) demonstrated the highest binding affinities, forming multiple hydrogen bond interactions with key residues such as Arg39, Tyr35, Ile33, and Ala11. These interactions were further stabilized by favorable steric contacts, suggesting strong potential activity. In contrast, most MMP derivatives displayed weaker or unfavorable docking scores, with positive re-rank values in some cases, indicating poor binding. Overall, MBL-103 and MBL-106 emerged as the most promising candidates, warranting further in vitro and in vivo evaluation. These findings highlight the utility of in-silico docking in prioritizing compounds for drug discovery pipelines and support the potential of camphor hydrazide derivatives as inhibitors of ATP-dependent DNA ligase.
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