title: The discovery of steroids and other novel FKBP inhibitors using a molecular docking program.
abstract: The molecular docking computer program SANDOCK was used to screen small molecule three-dimensional databases in the hunt for novel FKBP inhibitors. Spectroscopic measurements confirmed binding of over 20 compounds to the target protein, some with dissociation constants in the low micromolar range. The discovery that FK506 binding protein is a steroid binding protein may be of wider biological significance. Two-dimensional NMR was used to determine the steroid binding mode and confirmed the interactions predicted by the docking program.
authors.affiliation: Structural Biochemistry Unit, Edinburgh University, Michael Swann Building, Edinburgh, Kings Buildings, EH9 3JR, UK.
authors.forename: P
authors.initials: P
authors.lastname: Burkhard
authors.forename: U
authors.initials: U
authors.lastname: Hommel
authors.forename: M
authors.initials: M
authors.lastname: Sanner
authors.forename: M D
authors.initials: MD
authors.lastname: Walkinshaw
mesh_terms: D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006860:Hydrogen Bonding; D020104:Immunophilins / Q000037:antagonists & inhibitors*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D012984:Software; D013050:Spectrometry, Fluorescence / Q000379:methods; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D013256:Steroids; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins