Experiment Types: isCA-IM and isCA-SID-IM Cone isCA collision-induced unfolding/collapse/restructuring (CIx) plots for all four charge-reduced protein complexes are found as overlays within panel A of Figures . The respective RMSD plots for the averaged triplicates are found in the SI (Figures ). The RMSD values are high, ranging from 8 -11. This is likely due to collecting the CIU data on separate days, which allows for pressure fluctuations that affect drift time. While CCS calibration could correct for such fluctuations, calibration would not affect the overall trends that are described hereafter. The plots obtained for SA (Figure ), and CRP (Figure ) reflect decreases in drift time as a function of increasing cone voltage. This suggests that the proteins' quaternary structures were rearranged to smaller volumes due to isCA, as previously reported. CRP shows the most significant decrease in drift time at the highest cone voltages. Its structural rearrangement is partially attributable to its ring-shaped quaternary structure (inset, Figure ) collapsing inward on itself, and possibly includes interactions between the elongating monomer chain with remaining complex (inferred from fragmentation patterns and charge states). Unlike monomeric proteins, protein complexes, especially when charge-reduced, are less likely to undergo major unfolding/expansion. The CIx plot for PhosB (Figure and S4) does not possess noteworthy features that suggest significant quaternary rearrangement. Please note, the CIx plot overlay in Figure covers isCA voltages from 0 -100 V to align with the x-axis of the isCA -SID experiment. The full CIx plot, up to 160 V, for PhosB is found in Figure . While PhosB's plot does not contain noteworthy features, the drift time does decrease linearly with increasing cone voltage. This appears to result from increasing amounts of collisional de-adducting as a function of isCA. Examining the mass spectra collected with cone settings of 20 V and 160 V (not shown) revealed a -14 m/z shift between the two cone settings, which corresponds to an ~300 Da mass loss for the 21+ charge state. Overall, while the isCA CIx plots (panel A in Figures ) can be helpful in diagnosing sourceinduced quaternary structure rearrangements, this paper focuses on SID's utility as a diagnostic tool, as described below in a series of experiments where the isCA was varied, as denoted by isCA∆, and the SID energy was held constant, as denoted by SIDC. Based on that focus, the isCAΔ-SIDC plots in panel A of Figures contrast with the overlaid isCA CIx plots to show how SIDC results show diagnostic differences that may not be reflected in a CIx plot. Note that the CIx plot involves activation by CID only (no SID).