title: Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.
abstract: In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB.
authors.affiliation: Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service Tshwane Academic Division, Pretoria, South Africa.
authors.forename: Md Ataul
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria and National Health Laboratory Service Tshwane Academic Division, Pretoria, South Africa.|Division of Chemical Pathology, University of Cape Town, Pretoria, South Africa.
authors.forename: Tahir S
authors.identifier: 0000-0002-9982-9710
authors.initials: TS
authors.lastname: Pillay
mesh_terms: D027081:DNA Gyrase / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase
keywords: DNA gyrase; molecular docking; molecular dynamics; pharmacophore; virtual screening