Identification of potential riboflavin synthase inhibitors by virtual screening and molecular dynamics simulation studies

Riboflavin synthase is an important enzyme catalyzing the last step of riboflavin biosynthesis in microorganisms. Due to absolute dependency microbes this biosynthetic pathway coupled with its nonexistence humans, (RiS) considered as a prospective drug target. The for study was derived from Leptospira kmetyi, pathogenic bacterium locally isolated Malaysia. Leptospirosis, infectious disease caused by Leptospira, serious growing public health issue. Treatment leptospirosis antibiotics over time resulted evolution antibiotic resistance strains, thus requiring development newer but safe antimicrobial agents. In study, computational approach involving virtual screening followed molecular dynamics (MD) simulation implemented order identify possible inhibitors against synthase. model kmetyi predicted E. coli (1I8D) used target screen potential compounds ZINC database through screening. compound highest Glide score (?10.987 Kcal/mol) identified be ZINC21883831. Chemically it 2-[(2-chloro-4-fluoro-phenyl)methylsulfanyl]-7-phenyl-3,5-dihydropyrrolo[2,3-e]pyrimidin-4-one. top three docked complexes and apo-structures were subjected predict stabilities synthase-ligand complexes. Stability parameters including RMSD, RMSF, SASA Rg evaluated 60 ns MD trajectories. Insights provide promising starting points rational designs new effective anti-leptospirosis drugs.