Molecular recognition of agonist and antagonist for peroxisome proliferator-activated receptor-α studied by molecular dynamics simulations.
Peroxisome proliferator activated receptor-α (PPAR-α) is a ligand-activated transcription factor which plays important roles in lipid and glucose metabolism. The aim of this work is to find residues which selectively recognize PPAR-α agonists and antagonists. To achieve this aim, PPAR-α/13M and PPAR-α/471 complexes were subjected to perform molecular dynamics simulations. This research suggests that several key residues only participate in agonist recognition, while some other key residues only contribute to antagonist recognition. It is hoped that such work is useful for medicinal chemists to design novel PPAR-α agonists and antagonists.
State Key Laboratory of Crystal Materials, Shandong University, 27 Shanda Nanlu, Jinan 250100, China. lmyiop@sina.com.
Mengyuan
M
Liu
State Key Laboratory of Microbial Technology, Shandong University, 27 Shanda Nanlu, Jinan 250100, China. lswang@sdu.edu.cn.
Lushan
L
Wang
State Key Laboratory of Crystal Materials, Shandong University, 27 Shanda Nanlu, Jinan 250100, China. zhaoxian@icm.sdu.edu.cn.
Xian
X
Zhao
State Key Laboratory of Crystal Materials, Shandong University, 27 Shanda Nanlu, Jinan 250100, China. sunxun@icm.sdu.edu.cn.
Xun
X
Sun
D001665:Binding Sites; D020134:Catalytic Domain; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D047493:PPAR alpha / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D047493:PPAR alpha; D054852:Small Molecule Libraries