RT Journal Article SR Electronic T1 Three-dimensional models of neurotransmitter G-binding protein-coupled receptors. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 8 OP 15 VO 40 IS 1 A1 M F Hibert A1 S Trumpp-Kallmeyer A1 A Bruinvels A1 J Hoflack YR 1991 UL http://molpharm.aspetjournals.org/content/40/1/8.abstract AB Graphics computer-generated three-dimensional models of all G-binding protein-coupled receptors were built and analyzed. These models were defined using primary sequence comparisons, secondary structure predictions, and three-dimensional homology building, taking bacteriorhodopsin as a template. The transmembrane region of the dopamine D2, serotonin 5-hydroxytryptamine2, noradrenaline alpha 2, adrenaline beta 2, and acetylcholine m2 receptors were chosen as prototypes and explored in detail. In this report, we localize the ligand binding site and identify all the residues likely to be responsible for receptor affinity, selectivity, stereospecificity, and efficacy. The precise nature of the important physicochemical interactions between different residue side chains or between the ligand and the adjacent amino acids is also discussed. The models are in agreement with published data obtained from mutagenesis and labeling studies and represent important working hypotheses to direct future mutagenesis studies. They also enable structure-activity relationship studies and more rational drug design.