Novel and potent inhibitors for dihydropteroate synthase of .

An endless drug-resistant strains of and multitudinous drug reactions are obstacles in the treatment of infections, thereby ambitious novel proof-of-concept for inhibitor design was practiced in advancement of medication. Dihydropteroate synthase (DHPS) is an alluring target that plays a great role in folate synthesis pathway essential for amino acids biosynthesis was selected for designing novel drugs to prevent infections caused by pathogenic . In the present study, a reliable tertiary structure of DHPS in complex with inhibitor 6MB was constructed by Modeler 9v19. DrugBank compounds of DHPS, published inhibitors, and co-crystal ligand (6MB) were docked against DHPS. The best docked compounds were screened against 28.5 million compounds resulted 1186 structural analogs. Virtual screening workflow and quantum polarized ligand dockings of these compounds against DHPS resulted three leads that showed better XP Gscores, ADME properties, and binding-free energies compared to 6MB, DrugBank compounds, and published inhibitors. The proposed leads were also validated by receiver operative characteristic (ROC) curve metrics in the presence of thousand decoys and the best docked existing compounds against DHPS. Long-range molecular dynamics (MD) simulations for 100 ns were executed after post-docking evaluations. Trajectory analysis showed the lead-DHPS docking complex's inter-molecular interactions were stable throughout the entire runtime of MD simulations than 6MB-DHPS complex and Eliglustat-DHPS complex. The study outcomes showed good competitive binding propensity and active-tunneling of leads over the existing inhibitors, thereby these leads could be ideal inhibitors against DHPS to target .