Agonist-PPAR gamma interactions: Molecular modeling study with docking approach

摘要

Docking simulation of 18 agonists with the ligand binding pocket (LBP) of PPARgamma has been performed. The binding conformations and binding affinities of these agonists were obtained by use of the flexible docking protocol FlexX. Test compound calculations indicated that FlexX can reproduce the binding conformation of the crystal structure (root mean square deviation = 1.43 Angstrom); moreover, the predicted binding affinities correlate well with the activities of these agonists. The interaction model and pharmacophore of PPARgamma agonists were derived and the difference in biologic activities of these agonists can be well explained. The PPARgamma agonists must have both polar head and the hydrophobic tail, which form hydrogen bonds and hydrophobic contacts with hydrophilic and hydrophobic regions of the LBP of PPARgamma, respectively. In addition, a suitable linker is also necessary. (C) 2003 Wiley Periodicals, Inc. [References: 16]