The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120)
作者： Brian D. Hudson , Bharat Shimpukade , Graeme Milligan , Trond Ulven
关键词: Receptor 、 Binding site 、 Structure–activity relationship 、 alpha-Linolenic acid 、 GPR120 、 Homology modeling 、 Biochemistry 、 Stereochemistry 、 Fatty acid 、 Chemistry 、 Agonist
摘要: The long-chain fatty acid receptor FFA4 (previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. This study examines first time detailed mode binding both synthetic agonist ligands at by integrating molecular modeling, mutagenesis, ligand structure-activity relationship approaches in an iterative format. In doing so, residues required agonists to have been identified. has allowed refinement well validated model ligand-FFA4 interaction that will be invaluable identification future development this therapeutic target. reliably predicted effects substituent variations on potency, it was also able predict qualitative effect site mutations majority cases.
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