Flexible ligand recognition of peroxisome proliferator-activated receptor-γ (PPARγ)

摘要: The peroxisome proliferator-activated receptor-γ (PPARγ) is a direct pharmacological target for drugs that enhance insulin sensitivity and are used clinically the treatment of type II diabetes. Because specificity ligand recognition lower PPARγ than other nuclear receptors, can bind larger variety types. In order to elucidate why so flexible, we performed correlated fragment molecular orbital calculations complexes each two distinctive ligands, rosiglitazone farglitazar. We found quite different patterns binding these ligands. ligand-binding system rosiglitazone, drug in common clinical use, based mainly on local electrostatic interactions around thiazolidine ring, whereas both van der Waals dispersion with hydrophobic residues required farglitazar PPARγ. suggest development novel ligands will require adequately pharmacophores.