title: Ligand-based pharmacophore modelling and screening of DNA minor groove binders targeting Staphylococcus aureus.
abstract: The recognition of DNA by small molecules is of special importance in the design of new drugs. Many natural and synthetic compounds have the ability to interact with the minor groove of DNA. In the present study, identification of minor groove binding compounds was attained by the combined approach of pharmacophore modelling, virtual screening and molecular dynamics approach. Experimentally reported 32 minor groove binding compounds were used to develop the pharmacophore model. Based on the fitness score, best three pharmacophore hypotheses were selected and used as template for screening the compounds from drug bank database. This pharmacophore-based screening provides many compounds with the same pharmacological properties. All these compounds were subjected to four phases of docking protocols with combined Glide-quantum-polarized ligand docking approach. Molecular dynamics results indicated that selected compounds are more active and showed good interaction in the binding site of DNA. Based on the scoring parameters and energy values, the best compounds were selected, and antibacterial activity of these compounds was identified using in vitro antimicrobial techniques.
authors.affiliation: Bioinformatics Centre (BIF), PG and Research Department of Biotechnology and Bioinformatics, Holy Cross College (Autonomous), Tiruchirappalli, 620002, Tamil Nadu, India.
authors.forename: Periyasamy
authors.initials: P
authors.lastname: Vijayalakshmi
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Selvaraj
authors.forename: Raja Mohmed Beema
authors.initials: RM
authors.lastname: Shafreen
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Shunmugiah Karutha
authors.initials: SK
authors.lastname: Pandian
authors.forename: Pitchai
authors.initials: P
authors.lastname: Daisy
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D004247:DNA
keywords: MIC; QM/MM docking; Staphylococcus aureus; molecular dynamics; pharmacophore modelling