In a similar vein, Dr. Thomas Schmidt’s (NIH, NIDDK) projects involved GPCRs (G-protein coupled receptors), an important class of proteins that mediate cellular responses to stimuli and present an attractive target for drug development. Specifically, Schmidt used a global analysis method to elucidate the equilibrium of a monomer/dimer GPCR system governed by ligand interactions. His work reiterated the ability of EPR to gather deep insights into the whole of a biological process – investigating structure, dynamics, conformations, and kinetics all at once. On a technical level, the experimentalist in me appreciated a clever scheme in which he filtered out contributions from the monomers or dimers in his distance measurements by manipulating the differences in relaxation rates of the two species – an idea that may prove extremely valuable in efforts to deconvolute complicated multimodal distance distributions.

Finally, the work of Prof. Bela Bode (University of St. Andrews) pushed the boundaries of sensitivity in EPR measurements. In short, he showed that such measurements could be achieved on protein systems with concentrations as low as 50 nM. Typical EPR spectroscopy uses protein concentrations in the 100 μM range – 3-4 orders of magnitude higher. Lowering that limit is hugely important when transitioning from establishing methodologies on model proteins to collecting data on real, biologically relevant systems. Model systems are often chosen for their good behavior and ease of manipulation, such that generating 100 μM of such a protein can be a routine task. Not all – few, in fact – proteins are so polite, and lower the threshold of protein necessary will make previously prohibitively tricky macromolecules accessible by EPR.