Structural genomics of GPCRs

G protein-coupled receptors (GPCRs) are targets for 60–70% of drugs in development today. Traditionally, the drug discovery process has relied on screening of chemical compounds to identify novel and more-efficient drug molecules. Structure-based drug design, however, provides a targeted approach but has been severely hampered by limited knowledge of high-resolution structures of GPCRs owing to the difficulties encountered in their expression, purification and crystallization. In addition to individual laboratories studying specific GPCRs, structural genomics initiatives have been established as large networks with a wide range of expertise in protein expression, purification and crystallography. Several of these national and international consortia have included GPCRs in their programs. Milligram quantities of GPCRs can now be expressed in several expression systems and purified to high homogeneity. However, success in crystallization still requires major technological improvement.