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Agonist–PPARγ interactions: Molecular modeling study with docking approach
Author(s) -
Xu Xiao Ying,
Cheng Feng,
Shen Jian Hua,
Luo Xiao Min,
Chen Li Li,
Yue Li Duo,
Du Yi,
Ye Fei,
Jiang Shan Hao,
Zhu Da Yuan,
Jiang Hua Liang,
Chen Kai Xian
Publication year - 2003
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.10575
Subject(s) - pharmacophore , chemistry , docking (animal) , hydrogen bond , binding affinities , molecular dynamics , stereochemistry , hydrophobic effect , linker , affinities , binding pocket , agonist , computational chemistry , binding site , receptor , molecule , biochemistry , organic chemistry , medicine , nursing , computer science , operating system
Abstract Docking simulation of 18 agonists with the ligand binding pocket (LBP) of PPARγ 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 Å); moreover, the predicted binding affinities correlate well with the activities of these agonists. The interaction model and pharmacophore of PPARγ agonists were derived and the difference in biologic activities of these agonists can be well explained. The PPARγ 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 PPARγ, respectively. In addition, a suitable linker is also necessary. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 405–410, 2003