Abstract
G-protein coupled receptors (GPCRs) are the largest single family of signaling molecules in mammals and represent approximately 2-3% of all genes in the human genome. Estimates of the total number of GPCR genes in the human genome range from about 750 to 1000. GPCRs mediate signaling by a wide variety of ligands including amino acids, ions, biogenic amines, peptides, glycoproteins, light, pheromones, and odorants. There are presently only a handful of GPCRs whose structures have been elucidated. Of these, the mGluR1 subtype of metabotropic glutamate receptor (mGluR) and rhodopsin are the most widely used in modeling GPCRs. In the case of mGluR1, the three-dimensional structure of the extracellular ligand binding domain of the molecule has been solved, while the crystallographic data for rhodopsin encompasses the whole protein in the ground state with bound 11-cis-retinal. In this review, we discuss the use of homology modeling to investigate the structures and functions of GPCRs. We illustrate the use of homology modeling with a particular emphasis on ligand and drug binding sites in the Family C subfamily of GPCRs.
Keywords: Homology modeling, ligand-receptor interaction, ligand docking, mGluR, Family C GPCRs, cysteine-rich domain, allosteric modulato
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