Molecular recognition of long chain fatty acids by peroxisome proliferator-activated receptor alpha

作者：Gani Osman A B S M; Sylte Ingebrigt^*

来源：Medicinal Chemistry Research, 2009, 18(1): 8-19.

DOI：10.1007/s00044-008-9102-7

• Hyperlipidemia
• PPARalpha
• Long chain fatty acids
• Binding affinity predictions
• Molecular interactions

In the present study, flexible ligand docking and multiple scoring were used to study the binding of long-chain fatty acid (LCFAs) to the peroxisome proliferator-activated receptor alpha (PPAR alpha). The calculations indicated that LCFAs bind PPAR alpha in nanomolar affinities, which is in agreement with the intracellular concentrations of LCFAs. Calculated binding affinities were linearly related with the chain length up to 20 carbon atoms. The best correlation between the rank order of experimentally detected binding affinities and the predicted scores was found with the internal coordinate mechanics (ICM) binding energy method. This study contributes molecular insight into the binding process, which is of pivotal importance for designing new ligands interfering with lipid and glucose homeostasis.

• 出版日期2009-2
• 单位河北医科大学