Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems,Chemical Reviews

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Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems
Chemical Reviews ( IF 51.4 ) Pub Date : 2021-09-07 , DOI: 10.1021/acs.chemrev.1c00279
Ellie I James ₁ , Taylor A Murphree ₁ , Clint Vorauer ₁ , John R Engen ₂ , Miklos Guttman ₁

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Solution-phase hydrogen/deuterium exchange (HDX) coupled to mass spectrometry (MS) is a widespread tool for structural analysis across academia and the biopharmaceutical industry. By monitoring the exchangeability of backbone amide protons, HDX-MS can reveal information about higher-order structure and dynamics throughout a protein, can track protein folding pathways, map interaction sites, and assess conformational states of protein samples. The combination of the versatility of the hydrogen/deuterium exchange reaction with the sensitivity of mass spectrometry has enabled the study of extremely challenging protein systems, some of which cannot be suitably studied using other techniques. Improvements over the past three decades have continually increased throughput, robustness, and expanded the limits of what is feasible for HDX-MS investigations. To provide an overview for researchers seeking to utilize and derive the most from HDX-MS for protein structural analysis, we summarize the fundamental principles, basic methodology, strengths and weaknesses, and the established applications of HDX-MS while highlighting new developments and applications.

中文翻译：

氢/氘交换质谱的进展和对具有挑战性的生物系统的追求

溶液相氢/氘交换 (HDX) 与质谱 (MS) 耦合是学术界和生物制药行业结构分析的广泛工具。通过监测骨架酰胺质子的可交换性，HDX-MS 可以揭示整个蛋白质的高阶结构和动力学信息，可以跟踪蛋白质折叠途径，绘制相互作用位点，并评估蛋白质样品的构象状态。氢/氘交换反应的多功能性与质谱法的灵敏度相结合，使研究极具挑战性的蛋白质系统成为可能，其中一些无法使用其他技术进行适当的研究。过去三年的改进不断提高通量、稳健性，并扩大了 HDX-MS 研究的可行范围。

更新日期：2021-09-07

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