THE IMS PARADOX: A PERSPECTIVE ON STRUCTURAL ION MOBILITY-MASS SPECTROMETRY

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. (c) 2020 John Wiley & Sons Ltd. Mass Spec Rev

Automated summary

Studies on large proteins, protein complexes, and membrane protein complexes present new challenges in terms of increased ion mobility and mass spectrometry resolution. The development of IM-MS techniques has shown promising results in analyzing complex biomolecular structures and retaining solution phase conformations in gas phase ions. The integration of Fourier-transform IM-MS instruments has revolutionized the field by providing first-principles determinations of collision cross sections and enhancing the capabilities of native MS/IM-MS techniques.