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.