Computational Strategies and Challenges for Using Native Ion Mobility Mass Spectrometry in Biophysics and Structural Biology

Native mass spectrometry (MS) allows the interrogation of structural aspects of macromolecules in the gas phase, under the premise of having initially maintained their solution-phase non-covalent interactions intact. In the more than 25 years since the first reports, the utility of native MS has become well established in the structural biology community. The experimental and technological advances during this time have been rapid, resulting in dramatic increases in sensitivity, mass range, resolution, and complexity of possible experiments. As experimental methods are improved, there have been accompanying developments in computational approaches for analysing and exploiting the profusion of MS data in a structural and biophysical context. Here, based on discussions within the EU COST Action BM1403 on Native MS and Related Methods for Structural Biology with broad participation from Europe and North America, we consider the computational strategies currently being employed by the community, aspects of best practice, and the challenges that remain to be addressed.