The bacterial DNA gyrase is an attractive target to identify the novel antibacterial agents. The flavonoid derivatives possess various biological activities such as antimicrobial, anti-inflammatory and anticancer activities. The aim of present study is to identify the potential molecule from flavonoid derivatives against Staphylococcus aureus using atomistic simulation namely Molecular Docking, Quantum Chemical and Molecular Dynamics. The molecules Cpd58, Cpd65 and Cpd70 are identified as potential molecules through molecular docking approaches by exploring through the N - H…O hydrogen bonding interactions with Asn31 and Glu35 of Gyrase B. To confirm the intramolecular charge transfer in the flavonoid derivatives, Frontier Molecular Orbital (FMO) calculation was performed at M06/6-31g(d) level in gas phase. The lowest HOMO-LUMO gap was calculated for Cpd58, Cpd65 and Cpd70 among the selected compounds used in this study. Molecular dynamics simulation were carried out for Cpd58 and Cpd70 for a time period of 50 ns and found to be stable throughout the analysis. Therefore, the identified compounds are found to be a potent inhibitor for GyrB of S. aureus that can be validated by experimental studies. Communicated by Ramaswamy H. Sarma.
Keywords: ADME profile; DFT; DNA gyrase; HOMO-LUMO; M06; Staphylococcus aureus; flavonoids; free energy calculations; molecular docking; molecular dynamics simulation.