Advances in the application of NMR to the study of GPCRs and ligand-GPCR interactions.

Introduction: GPCRs are targeted by nearly one-third of FDA-approved drugs and are therefore of great interest in drug discovery pursuits. Nuclear magnetic resonance (NMR) builds upon our understanding of the structural biology of GPCRs by helping to identify dynamic facets of ligand engagement, activation, and G protein coupling, often through the identification of an ensemble.

Areas covered: The basic facets of NMR spectroscopy and relaxation experiments (e.g. CPMG, WaterLOGSY, STD) are described as they pertain to the study of structure activity relationships (SAR), ligand-fragment interaction dynamics, and fragment-based drug discovery. This article is based on literature searches that have utilized ISI Web of Knowledge, MEDLINE, and Google Scholar.

Expert opinion: The structural biology of GPCRs and their associated complexes are rapidly advancing, particularly via cryoEM techniques which provide high-resolution structures and additional insights into minor states represented into the ensemble. Nevertheless, there is still an important niche for NMR methods to capture in terms of the delineation of detailed and physiologically representative ensembles of functional states and their associated dynamics.