Complete GPCR Target List >>
Representative Structural Coverage of the GPCR Family
CMPD will attempt to determine the structure of representative GPCRs and their co-crystals with ligands. The long range goal is to develop a better understanding of the structure-function relationship in GPCRs. Ultimately enough structures will be determined to provide a fine sampling of the various GPCR sequence families and, thus, enable reliable modeling and predictive docking studies of other close family members. Structures of receptors in complex with different ligands will be essential for developing a better understanding of their binding properties. Ultimately, this newly acquired knowledge can then be used to validate and to generate hypothesis regarding GPCRs mechanisms of action (e.g., in signal processing pathways). These new structures will have an enormous impact on furthering our understanding of a number of diseases and most probably will help accelerate success rates in drug discovery and therapeutics development studies.
These challenging goals will be achieved through the use of an established HT membrane protein pipeline, developed and operated in the Stevens and Kuhn laboratories. This pipeline is powered by a number of key technologies that have also been developed in our laboratories.
In the next five years, we propose to study about 100 target receptors and expect to solve the structures of 15-20 unique targets.
We also plan to solve at least 3 co-crystal structures per target of its complex with a relevant ligand (e.g. antagonists, agonists, inverse agonists, allosteric modulators).