Normal mode analysis as a prerequisite for drug design: application to matrix metalloproteinases inhibitors.
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.
Floquet
Nicolas
N
Institut de Chimie des Substances Naturelles, ICSN, CNRS UPR-2301, Bat. 27 Avenue de la Terrasse, 91198 Gif sur Yvette, France.
Marechal
Jean-Didier
JD
Badet-Denisot
Marie-Ange
MA
Robert
Charles H
CH
Dauchez
Manuel
M
Perahia
David
D
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
D011480:Protease Inhibitors; D019278:Matrix Metalloproteinase 3