Studies of large proteins, protein complexes, and membrane protein complexes pose new challenges, most notably the need for increased ion mobility (IM) and mass spectrometry (MS) resolution. This review covers evolutionary developments in IM‐MS in the authors' and key collaborators' laboratories with specific focus on developments that enhance the utility of IM‐MS for structural analysis. IM‐MS measurements are performed on gas phase ions, thus “structural IM‐MS” appears paradoxical—do gas phase ions retain their solution phase structure? There is growing evidence to support the notion that solution phase structure(s) can be retained by the gas phase ions. It should not go unnoticed that we use “structures” in this statement because an important feature of IM‐MS is the ability to deal with conformationally heterogeneous systems, thus providing a direct measure of conformational entropy. The extension of this work to large proteins and protein complexes has motivated our development of Fourier‐transform IM‐MS instruments, a strategy first described by Hill and coworkers in 1985 (Anal Chem, 1985, 57, pp. 402–406) that has proved to be a game‐changer in our quest to merge drift tube (DT) and ion mobility and the high mass resolution orbitrap MS instruments. DT‐IMS is the only method that allows first‐principles determinations of rotationally averaged collision cross sections (CSS), which is essential for studies of biomolecules where the conformational diversities of the molecule precludes the use of CCS calibration approaches. The Fourier transform‐IM‐orbitrap instrument described here also incorporates the full suite of native MS/IM‐MS capabilities that are currently employed in the most advanced native MS/IM‐MS instruments. © 2020 John Wiley & Sons Ltd. Mass Spec Rev

中文翻译：

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IMS 悖论：结构离子淌度-质谱法的观点

对大型蛋白质、蛋白质复合物和膜蛋白复合物的研究提出了新的挑战，尤其是需要提高离子迁移率 (IM) 和质谱 (MS) 分辨率。这篇综述涵盖了作者和主要合作者实验室中 IM-MS 的进化发展，特别关注增强 IM-MS 在结构分析中的效用的发展。IM-MS 测量是在气相离子上进行的，因此“结构 IM-MS”似乎是矛盾的——气相离子是否保留其溶液相结构？越来越多的证据支持气相离子可以保留溶液相结构的观点。不应忽视我们在此声明中使用“结构”，因为 IM-MS 的一个重要特征是能够处理构象异构系统，从而提供构象熵的直接测量。将这项工作扩展到大蛋白质和蛋白质复合物，推动了我们开发傅里叶变换 IM-MS 仪器，这是 Hill 及其同事在 1985 年首次描述的一种策略 ( Anal Chem , 1985, 57, pp. 402–406) 已被证明是我们寻求合并漂移管 (DT) 和离子淌度以及高质量分辨率轨道阱 MS 仪器的游戏规则改变者。DT-IMS 是唯一允许第一性原理确定旋转平均碰撞截面 (CSS) 的方法，这对于分子的构象多样性排除使用 CCS 校准方法的生物分子的研究至关重要。此处描述的傅立叶变换-IM-orbitrap 仪器还集成了目前在最先进的原生 MS/IM-MS 仪器中使用的全套原生 MS/IM-MS 功能。© 2020 John Wiley & Sons Ltd. 质谱修订版