Talk title: Polypharmacology: A Feature, Not A Bug? Speaker: Prof. Brian Shoichet, UCSF Date: 2013-01-17 Time: 18:00:00 Location: UCSF Mission Bay 600 16th St. Byers Hall, Room 212 San Francisco, CA 94158 Schedule: 6 -- 7 pm: check-in & networking (pizza and wine provided) 7 -- 8 pm: presentation 8 -- 8:30 pm: informal discussions & networking Talk Abstract: Protein classification typically uses structural, sequence, or functional similarity. Here we explore an organization by ligand similarity, focusing on class A GPCRs. Comparing a ligand-based and sequence-based dendograms, we identified GPCRs that were distantly linked by sequence but neighbors by ligand similarity. Experimental testing of the ligands predicted to link three of these new pairs confirmed the predicted association, with potencies ranging from the low-nanomolar to low-micromolar. We also predicted hundreds of non-GPCRs closely related to GPCRs by ligand similarity, including the CXCR2 chemokine receptor to casein kinase I, the cannabinoid receptors to epoxide hydrolase 2, and the ?2 adrenergic receptor to phospholipase D, which we confirmed experimentally. Ligand similarities among these targets may reflect the conservation of identical ligands among unrelated receptors, which signal in different time domains. The method integrates these apparently unrelated receptors into chemically coherent circuits, and suggests which of these receptors may be targeted by individual ligands.