title: Identification of novel gyrase B inhibitors as potential anti-TB drugs: homology modelling, hybrid virtual screening and molecular dynamics simulations.
abstract: Using an integrated computational approach involving homology modelling, pharmacophore/structure-based virtual screening, molecular dynamics simulations and per-residue energy contribution, 10 compounds were proposed as potential TB inhibitors. Via validated docking calculations, binding free energy calculations showed that the proposed compounds presented better binding affinity with DNA gyrase B when compared to novobiocin. The compiled in silico approach employed in this study may serve as a useful tool in the process of the design and development of drugs, not only against TB, but also for a wide range of biological systems.
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa.
authors.forename: Yushir
authors.initials: Y
authors.lastname: Maharaj
authors.forename: Mahmoud E S
authors.initials: ME
authors.lastname: Soliman
mesh_terms: D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D017076:Computer-Aided Design; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase
keywords: Gyrase B inhibitors; computer-aided drug design; hybrid virtual screening