Effects of Charge State, Charge Distribution, and Structure on the Ion Mobility of Protein Ions in Helium Gas: Results from Trajectory Method Calculations.

Collision cross section (Ω) values of gas-phase ions of proteins and protein complexes are used to probe the structures of the corresponding species in solution. Ions of many proteins exhibit increasing Ω-values with increasing charge state but most Ω-values calculated for protein ions have used simple collision models that do not explicitly account for charge. Here we use a combination of ion mobility mass spectrometry experiments with helium gas and trajectory method calculations to characterize the extents to which increases in experimental Ω-values with increasing charge state may be attributed to increased momentum transfer concomitant with enhanced long-range interactions between the protein ion and helium atoms. Ubiquitin and C-to-N terminally linked diubiquitin ions generated from different solution conditions exhibit more than a 2-fold increase in Ω with increasing charge state. For native and energy-relaxed models of the proteins and most methods for distributing charge, Ω-values calculated using the trajectory method increase by less than 1% over the range of charge states observed from typical solution conditions used for native mass spectrometry. However, the calculated Ω-values increase by 10% to 15% over the full range of charge states observed from all solution conditions. Therefore, contributions from enhanced ion-induced dipole interactions with increasing charge state are significant but without additional structural changes can account for only a fraction of the increase in Ω observed experimentally. On the basis of these results, we suggest guidelines for calculating Ω-values in the context of applications in biophysics and structural biology.