Stereoselective binding of indomethacin ethanolamide derivatives to cyclooxygenase-1

We have used molecular modeling studies and molecular dynamics simulations to generate three-dimensional models for cyclooxygenase-1 complexes with a series of indomethacin ethanolamide derivatives. These studies provide a. plausible explanation for the stereoselective ligand binding preferences observed experimentally for these inhibitors and predict the general binding mode as well as specific structural details for the ligand-enzyme complexes. These studies provide insight into the nature of cyclooxygenase-1 interactions with a series of novel inhibitors and should help increase our understanding of key structural determinants for cyclooxygenase isozyme-selective inhibitor binding.