Parrill and Baker receive NIH R15 award
The National Institutes of Health recently funded a joint project between the Parrill and Baker research groups entitled "GPR88 Ligand Discovery". This three year R15 award totals $408,000. G protein-coupled receptors (GPCR) comprise a membrane protein family and are the primary cellular sensors for external chemical stimuli. The orphan GPCR, GPR88, plays an important role in motor coordination and learning, and has been genetically associated with schizophrenia and bipolar disorder. The proposed computational modeling-driven approach aims to identify the natural agonist of GPR88. This knowledge will open the door toward a better understanding of the molecular events that lead to these devastating psychiatric diseases. This project also aims to identify drug-like antagonists of GPR88 that may pave the way for new psychiatric disease treatments.
Superposition of crystal structures that serve as candidate modeling templates for GPR88. β1-adrenoceptor (orange ribbons), HT-1B serotonin receptor (magenta ribbons with yellow fusion partner), histamine H1 receptor (cyan ribbons with yellow fusion partner), dopamine D3 receptor (dark blue ribbons with yellow fusion partner). Left: Image of TM helices from within membrane. Right: image of extracellular loops (EL) from outside cell. Cyanopindolol from the β1-adrenoceptor crystal structure is shown as a spacefilling model to illustrate the position of the ligand binding pocket.