Docking studies on NSAID/COX-2 isozyme complexes using contact statistics analysis

• Published in: Journal of computer-aided molecular design Vol. 18; no. 11; pp. 683 - 696
• Main Authors: Ermondi, Giuseppe, Caron, Giulia, Lawrence, Raelene, Longo, Dario
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.11.2004
• Subjects: Algorithms; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Binding Sites; Crystallography, X-Ray; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - metabolism; Flurbiprofen - chemistry; Flurbiprofen - metabolism; Humans; Isoenzymes - chemistry; Isoenzymes - metabolism; Lactones - chemistry; Lactones - metabolism; Membrane Proteins; Models, Molecular; Models, Statistical; Molecular biology; Molecular Conformation; Molecular Structure; Nonsteroidal anti-inflammatory drugs; Pharmacology; Prostaglandin-Endoperoxide Synthases - chemistry; Prostaglandin-Endoperoxide Synthases - metabolism; Protein Binding; Pyrazoles - chemistry; Pyrazoles - metabolism; Statistical analysis; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfones - chemistry; Sulfones - metabolism
• ISSN: 0920-654X; 1573-4951
• DOI: 10.1007/s10822-004-6258-1

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.