title: Stereoselective binding of indomethacin ethanolamide derivatives to cyclooxygenase-1.
abstract: 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.
authors.affiliation: Department of Chemistry, Vanderbilt University, Center for Structural Biology, 5142 Biosciences/MRB III, Nashville, Tennessee 37232-8725, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Moth
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Prusakiewicz
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: Terry P
authors.initials: TP
authors.lastname: Lybrand
mesh_terms: D000818:Animals; D001665:Binding Sites; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D004983:Ethanolamines / Q000737:chemistry*; D006860:Hydrogen Bonding; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012756:Sheep; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D016861:Cyclooxygenase Inhibitors; D004983:Ethanolamines; D008024:Ligands; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin