Hydrogen/Deuterium exchange (HDX) has been applied, since the 1930s, as an analytical tool to study the structure and dynamics of (small) biomolecules. The popularity of using HDX to study proteins increased drastically in the last two decades due to the successful combination with mass spectrometry (MS). Together with this growth in popularity, several technological advances have been made, such as improved quenching and fragmentation. As a consequence of these experimental improvements and the increased use of protein‐HDXMS, large amounts of complex data are generated, which require appropriate analysis. Computational analysis of HDXMS requires several steps. A typical workflow for proteins consists of identification of (non‐)deuterated peptides or fragments of the protein under study (local analysis), or identification of the deuterated protein as a whole (global analysis); determination of the deuteration level; estimation of the protection extent or exchange rates of the labile backbone amide hydrogen atoms; and a statistically sound interpretation of the estimated protection extent or exchange rates. Several algorithms, specifically designed for HDX analysis, have been proposed. They range from procedures that focus on one specific step in the analysis of HDX data to complete HDX workflow analysis tools. In this review, we provide an overview of the computational methods and discuss outstanding challenges. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:649–667, 2017

中文翻译：

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氢/氘交换质谱的计算方法和挑战

自1930年代以来，氢/氘交换（HDX）已被用作研究（小）生物分子的结构和动力学的分析工具。在过去的二十年中，由于成功地与质谱（MS）相结合，使用HDX来研究蛋白质的普及率急剧上升。伴随着这种受欢迎程度的增长，已经取得了一些技术进步，例如改进的淬灭和破碎。由于这些实验性的改进和蛋白质HDXMS使用的增加，生成了大量复杂数据，需要进行适当的分析。HDXMS的计算分析需要几个步骤。蛋白质的典型工作流程包括鉴定（非）氘化的肽或研究中的蛋白质片段（局部分析），或整体鉴定出氘化蛋白质（全局分析）；确定氘化水平；估计不稳定的骨架酰胺氢原子的保护程度或交换率；对估计的保护范围或汇率进行统计上合理的解释。已经提出了几种专门为HDX分析设计的算法。它们的范围从专注于HDX数据分析中特定步骤的过程到完整的HDX工作流程分析工具。在这篇综述中，我们提供了计算方法的概述并讨论了突出的挑战。分级为4 +©2016 Wiley Periodicals，Inc.Mass Spec Rev 36：649–667，2017 对估计的保护范围或汇率进行统计上合理的解释。已经提出了几种专门为HDX分析设计的算法。它们的范围从专注于HDX数据分析中特定步骤的过程到完整的HDX工作流程分析工具。在这篇综述中，我们提供了计算方法的概述并讨论了突出的挑战。分级为4 +©2016 Wiley Periodicals，Inc.Mass Spec Rev 36：649–667，2017 对估计的保护范围或汇率进行统计上合理的解释。已经提出了几种专门为HDX分析设计的算法。它们的范围从专注于HDX数据分析中特定步骤的过程到完整的HDX工作流程分析工具。在这篇综述中，我们提供了计算方法的概述并讨论了突出的挑战。©2016 Wiley Periodicals，Inc.质谱Rev 36：649–667，2017 我们提供了计算方法的概述，并讨论了突出的挑战。分级为4 +©2016 Wiley Periodicals，Inc.Mass Spec Rev 36：649–667，2017 我们提供了计算方法的概述，并讨论了突出的挑战。分级为4 +©2016 Wiley Periodicals，Inc.Mass Spec Rev 36：649–667，2017