title: Docking studies on NSAID/COX-2 isozyme complexes using contact statistics analysis.
abstract: The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex) and rofecoxib (Vioxx). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes-and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, V.P. Giuria 9, 1-10125 Torino, Italy. giuseppe.ermondi@unito.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ermondi
authors.forename: Giulia
authors.initials: G
authors.lastname: Caron
authors.forename: Raelene
authors.initials: R
authors.lastname: Lawrence
authors.forename: Dario
authors.initials: D
authors.lastname: Longo
mesh_terms: D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism; D005480:Flurbiprofen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism; D013450:Sulfones / Q000737:chemistry / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; C102643:SC 558; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D005480:Flurbiprofen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide