title: Normal mode analysis as a prerequisite for drug design: application to matrix metalloproteinases inhibitors.
abstract: We demonstrate the utility of normal mode analysis in correctly predicting the binding modes of inhibitors in the active sites of matrix metalloproteinases (MMPs). We show the accuracy in predicting the positions of MMP-3 inhibitors is strongly dependent on which structure is used as the target, especially when it has been energy minimized. This dependency can be overcome by using intermediate structures generated along one of the normal modes previously calculated for a given target. These results may be of prime importance for further in silico drug discovery.
authors.affiliation: Institut de Chimie des Substances Naturelles, ICSN, CNRS UPR-2301, Bat. 27 Avenue de la Terrasse, 91198 Gif sur Yvette, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Floquet
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Marechal
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Badet-Denisot
authors.forename: Charles H
authors.initials: CH
authors.lastname: Robert
authors.forename: Manuel
authors.initials: M
authors.lastname: Dauchez
authors.forename: David
authors.initials: D
authors.lastname: Perahia
mesh_terms: D015195:Drug Design; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D019278:Matrix Metalloproteinase 3