The use of GPCR structures in drug design

Adv Pharmacol. 2011:62:1-36. doi: 10.1016/B978-0-12-385952-5.00011-7.


Structure-based drug discovery is routinely applied to soluble targets such as proteases and kinases. It is only recently that multiple high-resolution X-ray structures of G protein-coupled receptors (GPCRs) have become available. Here we review the technology developments that have led to the recent plethora of GPCR structures. These include developments in protein expression and purification as well as techniques to stabilize receptors and crystallize them. We discuss the findings derived from the new structures with regard to understanding GPCR function and pharmacology. Finally, we examine the utility of structure-based drug discovery approaches including homology modeling, virtual screening, and fragment screening for GPCRs in the context of what has been learnt from other target classes.

Publication types

  • Review

MeSH terms

  • Crystallography, X-Ray
  • Drug Design*
  • Humans
  • Models, Molecular
  • Receptors, G-Protein-Coupled / chemistry*


  • Receptors, G-Protein-Coupled