生物大分子如蛋白质、核酸和碳水化合物包含杂原子键合的氢，它们与溶剂中的氢发生交换，时间范围从微秒到小时不等。在氢氘交换质谱（HDX-MS）中，利用这一交换过程提取有关生物分子结构和动态的信息。本综述聚焦于毫秒级时间尺度的HDX-MS测量，虽然比“常规”时间尺度（秒到小时）的HDX-MS更为罕见，但提供了研究弱结构物种、弱（或快速循环）结合相互作用和构象动力学微小变化的独特视角。这包括与癌症和淀粉样神经退行性疾病相关的内源性无序蛋白质和区域（IDP / IDR）。对于核酸和碳水化合物，可以阐明诸如异构体、茎和环等结构，并且可以评估整体结构的刚性。我们将简要概述快速HDX的技术发展，然后重点介绍各种应用，强调扩展HDX时间尺度的重要性，以提高吞吐量并捕捉更广泛的功能相关动态和结构变化。 © 2023作者。由波特兰出版社代表生化学会发布。

Biological macromolecules, such as proteins, nucleic acids, and carbohydrates, contain heteroatom-bonded hydrogens that undergo exchange with solvent hydrogens on timescales ranging from microseconds to hours. In hydrogen-deuterium exchange mass spectrometry (HDX-MS), this exchange process is used to extract information about biomolecular structure and dynamics. This minireview focuses on millisecond timescale HDX-MS measurements, which, while less common than 'conventional' timescale (seconds to hours) HDX-MS, provide a unique window into weakly structured species, weak (or fast cycling) binding interactions, and subtle shifts in conformational dynamics. This includes intrinsically disordered proteins and regions (IDPs/IDRs) that are associated with cancer and amyloidotic neurodegenerative disease. For nucleic acids and carbohydrates, structures such as isomers, stems, and loops, can be elucidated and overall structural rigidity can be assessed. We will provide a brief overview of technical developments in rapid HDX followed by highlights of various applications, emphasising the importance of broadening the HDX timescale to improve throughput and to capture a wider range of function-relevant dynamic and structural shifts.© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.