title: Thermodynamic computational approach to capture molecular recognition in the binding of different inhibitors to the DNA gyrase B subunit from Escherichia coli.
abstract: DNA gyrase subunit B, that catalyzes the hydrolysis of ATP, is an attractive target for the development of antibacterial drugs. This work is intended to rationalize molecular recognition at DNA gyrase B enzyme - inhibitor binding interface through the evaluation of different scoring functions in finding the correct pose and scoring properly 50 Escherichia coli DNA Gyrase B inhibitors belonging to five different classes. Improving the binding free energy calculation accuracy is further attempted by using rescoring schemes after short molecular dynamic simulations of the obtained docked complexes. These data are then compared with the corresponding experimental enzyme activity data. The results are analyzed from a structural point of view emphasizing the strengths and limitations of the techniques applied in the study.
authors.affiliation: Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Liane
authors.initials: L
authors.lastname: Saíz-Urra
authors.forename: Miguel Ángel Cabrera
authors.initials: MÁ
authors.lastname: Pérez
authors.forename: Matheus
authors.initials: M
authors.lastname: Froeyen
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D027081:DNA Gyrase / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry* / Q000201:enzymology; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012107:Research Design; D013816:Thermodynamics; D059005:Topoisomerase II Inhibitors / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; D027081:DNA Gyrase