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 ²H static NMR methods applicable for studies of microsecond to millisecond motional modes in proteins, particularly rotating frame relaxation dispersion (R_1ρ), 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 ¹⁵N/¹³C/¹H nuclei, these techniques provide powerful tools for studies of biologically relevant timescale dynamics in disordered domains in the solid state.

蛋白质的慢时标动力学对于配体结合、酶催化、蛋白质折叠和错误折叠调节以及蛋白质-蛋白质和蛋白质-核酸相互作用等多种生物功能至关重要。在这篇综述中，我们重点关注² H 静态 NMR 方法的实验和理论发展，这些方法适用于研究蛋白质的微秒到毫秒运动模式，特别是旋转框架弛豫色散 ( R _1ρ )、四极 Carr-Purcell-Meiboom-Gill (QCPMG) ) 弛豫色散和四极化学交换饱和转移 NMR 实验 (Q-CEST)。通过从淀粉样蛋白-β原纤维中选择的应用，我们展示了这些方法的互补性，通过使用选择性氘标记来阐明非晶态固态无序域中构象整体的复杂性。结合¹⁵ N/ ¹³ C/ ¹ H 核弛豫色散主链测量的最新进展，这些技术为研究固态无序域中的生物相关时间尺度动力学提供了强大的工具。