Department of Chemistry and Biochemistry
Physical Chemistry Seminar Series

Professor James Prell, University of Oregon

Measuring Energy Landscapes for Biomolecules  with Native Mass Spectrometry

Advances in instrumentation for structural biology and bioanalytical chemistry have enabled the study of ever larger and more dynamic biomolecules and biomolecular complexes. Native ion mobility-mass spectrometry offers advantages for interrogating small, heterogeneous, and dynamic samples while preserving much high-order structure even as analytes are transferred from buffered aqueous solution into the gas phase. Deliberate, precisely controlled heating of the resulting ions inside the mass spectrometer can result in collision-induced dissociation and/or unfolding (CID/U) of non-covalent complexes, revealing structural information that can be exceptionally difficult to access with conventional techniques. However, to date, a quantitative understanding of CID and CIU as a function of acceleration potentials, gas pressure and identity, and other factors has been lacking.

Our recently introduced software suite (IonSPA) can quantitatively predict ion heating, cooling, and motion in such experiments and be used to determine dissociation and unfolding barriers, which are crucial information for interpreting experimental data in terms of structures and chemical properties of the solution-phase biomolecules. We further show that this model can be used to reconcile data acquired using very different instrumentation from a variety of vendors, a key step in tethering these readily available experiments to a universal physical chemistry framework.