Abstract
A computational protocol has been devised to relate 7TM receptor proteins (GPCRs) with respect to physicochemical features of the core ligand-binding site as defined from the crystal structure of bovine rhodopsin. The identification of such receptors that already are associated with ligand information (e.g., small molecule ligands with mutagenesis or SAR data) is used to support structure-guided drug design of novel ligands. A case targeting the newly identified prostaglandin D2 receptor CRTH2 serves as a primary example to illustrate the procedure.
MeSH terms
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Animals
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Binding Sites / physiology
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Binding, Competitive / drug effects
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Biphenyl Compounds
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Cattle
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Computer Simulation*
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Drug Design*
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Hydrocarbons, Aromatic / pharmacology*
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Indomethacin / analogs & derivatives
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Indomethacin / chemistry
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Indomethacin / pharmacology
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Ligands
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Models, Biological
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Molecular Structure
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Receptors, G-Protein-Coupled / classification
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / metabolism
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Receptors, Prostaglandin / antagonists & inhibitors
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Receptors, Prostaglandin / metabolism
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Rhodopsin / chemistry*
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Structure-Activity Relationship
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Tetrazoles / chemistry
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Tetrazoles / pharmacology
Substances
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Benzimidazoles
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Biphenyl Compounds
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Hydrocarbons, Aromatic
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Ligands
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Receptors, G-Protein-Coupled
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Receptors, Immunologic
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Receptors, Prostaglandin
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Tetrazoles
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Rhodopsin
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candesartan
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Indomethacin
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prostaglandin D2 receptor