title: Binding modes and pharmacophore modelling of thermolysin inhibitors.
abstract: In the present paper 25 known thermolysin inhibitors were docked into thermolysin using the Internal Coordinate Mechanics (ICM) software. Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout program. The docking studies indicated that all 25 inhibitors coordinated the catalytic zinc in bidentate or monodentate geometry. A 'three-point' pharmacophore model was proposed which consisted of a hydrophobic group, a negative ionizable group and a hydrogen bond acceptor group. Finally the pharmacophore model has been tested against a small compound library containing 18 highly, moderately, less active as well as inactive compounds. The screening indicated that the pharmacophore model could, identify highly active compounds in front of inactive or less active ones.
authors.affiliation: Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037, Tromsø, Norway. mthkhan2002@yahoo.com
authors.forename: M T H
authors.initials: MT
authors.lastname: Khan
authors.forename: Y
authors.initials: Y
authors.lastname: Wuxiuer
authors.forename: I
authors.initials: I
authors.lastname: Sylte
mesh_terms: D001665:Binding Sites; D013820:Thermolysin / Q000037:antagonists & inhibitors*
chemical_list: D013820:Thermolysin