Structural ion mobility spectrometry: What can we really measure?

Advancing our understanding of biomolecular systems requires technologies that can unravel their intricate dynamics and structures. Mass spectrometry (MS) has emerged as a versatile technique for characterizing complex systems, yet its findings are most impactful when paired with structural methods such as NMR, X-ray crystallography, and microscopy. This Perspective examines how ion mobility-mass spectrometry (IM-MS) serves as a key connector between dynamic molecular behavior and high-resolution structural insights. Examples from recent research in our laboratory illustrate how IM-MS enhances the study of flexible peptides, transient protein assemblies, and metabolite aggregation. These studies highlight the method's ability to reveal properties inaccessible to single techniques. By integrating multiple approaches, researchers gain a more comprehensive view of biomolecular complexity, demonstrating the power of combining analytical methods to tackle open questions in structural biology. This approach reflects the collaborative and iterative nature of science, where diverse perspectives converge to deepen our understanding of the molecular world.