Recent developments in deuterium solid-state NMR for the detection of slow motions in proteins.

Slow timescale dynamics in proteins are essential for a variety of biological functions spanning ligand binding, enzymatic catalysis, protein folding and misfolding regulations, as well as protein-protein and protein-nucleic acid interactions. In this review, we focus on the experimental and theoretical developments of H static NMR methods applicable for studies of microsecond to millisecond motional modes in proteins, particularly rotating frame relaxation dispersion (R), quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) relaxation dispersion, and quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST). With applications chosen from amyloid-β fibrils, we show the complementarity of these approaches for elucidating the complexities of conformational ensembles in disordered domains in the non-crystalline solid state, with the employment of selective deuterium labels. Combined with recent advances in relaxation dispersion backbone measurements for N/C/H nuclei, these techniques provide powerful tools for studies of biologically relevant timescale dynamics in disordered domains in the solid state.