Functional dynamics of proteins revealed by solution NMR

► Solution NMR can analyze the dynamics of proteins over a wide range of timescales. ► Recent progresses in a variety of NMR techniques are reviewed. ► Relaxation dispersion and PRE are capable of discerning ‘invisible’ low-populated states. ► NMR applications to functionally relevant protein dynamics are also introduced. Solution NMR spectroscopy can analyze the dynamics of proteins on a wide range of timescales, from picoseconds to even days, in a site-specific manner, and thus its results are complementary to the detailed but largely static structural information obtained by X-ray crystallography. We review recent progresses in a variety of NMR techniques, including relaxation dispersion and paramagnetic relaxation enhancement (PRE), that permit the observation of the low-populated states, which had been ‘invisible’ with other techniques. In addition, we review how NMR spectroscopy can be used to elucidate functionally relevant protein dynamics.