Methodological improvements in both single particle cryo-electron microscopy (cryo-EM) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) mean that the two methods are being more frequently used together to tackle complex problems in structural biology. There are many benefits to this combination, including for the analysis of low-resolution density, for structural validation, in the analysis of individual proteins versus the same proteins in large complexes, studies of allostery, protein quality control during cryo-EM construct optimization, and in the study of protein movements/dynamics during function. As will be highlighted in this review, through careful considerations of potential sample and conformational heterogeneity, many joint studies have recently been demonstrated, and many future studies using this combination are anticipated.

单粒子冷冻电子显微镜 (cryo-EM) 和氢/氘交换质谱 (HDX-MS) 的方法学改进意味着这两种方法更频繁地一起使用来解决结构生物学中的复杂问题。这种组合有很多好处，包括分析低分辨率密度、结构验证、分析单个蛋白质与大型复合物中的相同蛋白质、变构研究、冷冻电镜构建优化期间的蛋白质质量控​​制、以及功能期间蛋白质运动/动力学的研究。正如本综述将强调的那样，通过仔细考虑潜在样本和构象异质性，最近已经证明了许多联合研究，并且预计将有许多使用这种组合的未来研究。