title: Theoretical studies on the inhibition mechanism of cyclooxygenase-2. Is there a unique recognition site?
abstract: The mechanism of binding of different nonsteroidal anti-inflammatory drugs to the cyclooxygenase active site of cyclooxygenase-2 (COX-2) has been studied by means of a wide range of theoretical techniques including molecular dynamics and free energy calculations. It is found that theoretical methods predict accurately the binding of different drugs based on different scaffolds. Calculations allow us to describe in detail the key recognition sites and to analyze how these recognition sites change depending on the scaffold of the drug. It is concluded that the recognition site of COX-2 is very flexible and can adapt its structure to very subtle structural changes in the drug.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Soliva
authors.forename: Carmen
authors.initials: C
authors.lastname: Almansa
authors.forename: Susana G
authors.initials: SG
authors.lastname: Kalko
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Luque
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001665:Binding Sites; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D011485:Protein Binding; D011720:Pyrazoles; D012997:Solvents / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry; D013450:Sulfones; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D011720:Pyrazoles; D012997:Solvents; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib