Evaluation of mechanical features and antibacterial potential of fluoroquinolone against β-ketoacyl-ACP synthases (FabB, FabF & FabH) via computational approaches

The synthesis of fatty acids, which are essential for the growth and survival of bacterial cells, is catalyzed by beta-keto acyl-ACP synthase I-III. Due to the significant differences between the bacterial ACP synthase enzyme and the mammalian enzyme, it may serve as a viable target for the development of potent anti-bacterial medications. In this study, a sophisticated molecular docking strategy was employed to target all three KAS enzymes. Initially, 1000 fluoroquinolone derivatives were obtained from PubChem database, along with the commonly used ciprofloxacin, and subjected to virtual screening against FabH, FabB, and FabF, respectively. Subsequently, molecular dynamics (MD) simulations were conducted to confirm the stability and reliability of the generated conformations. The compounds 155813629, 142486676, and 155567217 were found to exhibit potential molecular interactions against FabH, FabB, and FabF, respectively, with docking scores of -9.9, -8.9, and -9.9 kcal/mol. These scores outperformed the docking score of standard ciprofloxacin. Furthermore, MD simulations were used to assess the dynamic nature of molecular interactions in both physiological and dynamic settings. Throughout the simulated trajectory, all three complexes displayed favorable stability patterns. The findings of this investigation suggest that fluoroquinolone derivatives may serve as highly effective and selective inhibitors of the KAS enzyme.