Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand‐binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands. The receptor subtype selectivity of retinoid X and retinoic acid receptors for structurally different retinoids was investigated using a combination of classical molecular mechanics and quantum mechanical calculations. This type of receptor–ligand interaction analysis is useful for understanding the origin of receptor subtype selectivity and is a promising method for synthesizing and discovering subtype‐specific ligands in the field of drug discovery.