title: Structure-based drug design for G protein-coupled receptors.
abstract: Our understanding of the structural biology of G protein-coupled receptors has undergone a transformation over the past 5 years. New protein-ligand complexes are described almost monthly in high profile journals. Appreciation of how small molecules and natural ligands bind to their receptors has the potential to impact enormously how medicinal chemists approach this major class of receptor targets. An outline of the key topics in this field and some recent examples of structure- and fragment-based drug design are described. A table is presented with example views of each G protein-coupled receptor for which there is a published X-ray structure, including interactions with small molecule antagonists, partial and full agonists. The possible implications of these new data for drug design are discussed.
authors.affiliation: Heptares Therapeutics Ltd, BioPark, Welwyn Garden City, Hertfordshire, United Kingdom.
authors.forename: Miles
authors.initials: M
authors.lastname: Congreve
authors.affiliation: Heptares Therapeutics Ltd, BioPark, Welwyn Garden City, Hertfordshire, United Kingdom.
authors.forename: João M
authors.initials: JM
authors.lastname: Dias
authors.affiliation: Heptares Therapeutics Ltd, BioPark, Welwyn Garden City, Hertfordshire, United Kingdom.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Marshall
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry; D011968:Receptors, Histamine / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects
chemical_list: D011943:Receptors, Adrenergic, beta; D019718:Receptors, CXCR4; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018047:Receptors, Purinergic P1
keywords: Agonist; Antagonist; FBDD; Fragment; Fragment-based drug design; GPCR; SBDD; Structure-based drug design