Molecular modelling of D2-like dopamine receptors

• Published in: Biochemical journal Vol. 287; no. 1; pp. 277 - 282
• Main Authors: LIVINGSTONE, C. D, STRANGE, P. G, NAYLOR, L. H
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 01.10.1992
• Subjects: Amino Acid Sequence; Bacteriorhodopsins - chemistry; Biological and medical sciences; Cell receptors; Cell structures and functions; Computer Simulation; Dopamine - chemistry; Dopamine Agents - chemistry; Fundamental and applied biological sciences. Psychology; Ligands; Membrane Glycoproteins - ultrastructure; Models, Molecular; Molecular and cellular biology; Molecular Sequence Data; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Receptors, Dopamine - chemistry; Receptors, Dopamine - ultrastructure; Sequence Alignment; Vertebrata; Three dimensional model; Mammalia; Rat; Ligand; Dopamine receptor; Rodentia; Molecular interaction; Modeling; Computer aid; Intramolecular interaction
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2870277

Three-dimensional computer models of the rat D2, D3 and D4 dopamine receptor subtypes have been constructed based on the diffraction co-ordinates for bacteriorhodopsin, another membrane-bound protein containing seven transmembrane domains presumed to be arranged in a similar spatial orientation. Models were assembled by aligning the putative transmembrane domains of the dopamine receptors with those of bacteriorhodopsin using sequence similarities, and then superimposing these modelled alpha-helices on to the bacteriorhodopsin-derived co-ordinates. These models explore the potential hydrogen bonding, electrostatic and stacking interactions within the receptor which may be important for maintaining the conformation of these receptors, and thereby provide target sites for agonist binding. Proposed interactions between the catecholamine ligands and these receptors appear to account for the affinity, although not the specificity, of these agonist ligands for the different dopamine receptor subtypes. Such models will be useful for establishing structure-function relationships between ligands and the dopamine receptors, and may ultimately provide a template for the design of receptor-specific drugs.