A comparative docking study and the design of potentially selective MMP inhibitors.
As part of a program aimed at the design and synthesis of constrained MMP inhibitors, a survey of the reported X-ray and NMR structures of MMP/inhibitor complexes was performed, revealing mutations of key amino acids at different subsites between MMPs. A comparative study of fully automated docking programs AutoDock and DOCK in closely approximating the X-ray crystal structures of ten selected MMP inhibitors was performed. AutoDock proved to be highly reliable, efficient and predictive for a set of inhibitors with less than six atom types.
Hanessian
S
S
Department of Chemistry, Université de Montréal, QC, Canada. stephen.hanessian@umontreal.ca
Moitessier
N
N
Therrien
E
E
D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012984:Software; D013816:Thermodynamics
D046911:Macromolecular Substances; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases