NMR Spectroscopy in GPCR Drug Discovery

GPCRs are conformationally complex molecules. This conformational complexity contributes to the challenges of drug discovery: in identifying lead compounds, and in developing leads into selective, effective and safe drugs. Nuclear magnetic resonance spectroscopy (NMR) is a versatile tool that has the potential to provide high-resolution structural information about receptor-drug interactions and about the dynamic aspects of GPCR structure. NMR is routinely used in drug discovery for soluble protein targets; however, the application of NMR to GPCRs has not been practicable. This is primarily due to limitations in sample preparation (expression, isotope labeling, and purification) rather than limitations in NMR instrumentation and methodology. ConfometRx is developing methods to overcome current technical limitations in applying NMR spectroscopy as a drug discovery and development tool for GPCRs.