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Theoretical studies on the inhibition mechanism of cyclooxygenase-2. Is there a unique recognition site?

Posted June 8th, 2010 by pschmidtke
TitleTheoretical studies on the inhibition mechanism of cyclooxygenase-2. Is there a unique recognition site?
Publication TypeJournal Article
Year of Publication2003
AuthorsSoliva, R, Almansa C, Kalko SG, Luque FJ, Orozco M
JournalJournal of medicinal chemistry
Volume46
Issue8
Pagination1372 - 1382
Date Published2003/04/10/
KeywordsAlgorithms; Anti-Inflammatory Agents, Molecular; Prostaglandin-Endoperoxide Synthases/chemistry; Protein Binding; Pyrazoles; Solvents/chemistry; Sulfonamides/chemistry; Sulfones; Thermodynamics, Non-Steroidal/chemistry; Binding Sites; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors/chemistry; Isoenzymes/antagonists & inhibitors/chemistry; Lactones/chemistry; Models
AbstractThe 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.