Project 1 is responsible for achieving the Center‟s Aim 1 goals; the immediate goal of Aim 1 studies is the structure solution of 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.