Structure-based drug design for G protein-coupled receptors

Prog Med Chem. 2014;53:1-63. doi: 10.1016/B978-0-444-63380-4.00001-9.


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.

Keywords: Agonist; Antagonist; FBDD; Fragment; Fragment-based drug design; GPCR; SBDD; Structure-based drug design.

Publication types

  • Review

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • Drug Discovery*
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, CXCR4 / drug effects
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, Histamine / drug effects
  • Receptors, Purinergic P1 / drug effects


  • Receptors, Adrenergic, beta
  • Receptors, CXCR4
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Purinergic P1