Materials and Sample Preparation. More details on materials and selected protein complexes can be found in the Supporting Information. All protein complexes were buffer exchanged into 200 mM ammonium acetate using size exclusion chromatography spin columns (Bio-Rad) with a 6 kDa mass cutoff. Complexes were charge-reduced using 20% (v/v) triethylammonium acetate (TEAA) because it has been observed that lower charge state protein complexes' ions generally maintain more native-like structures, and SID dissociates these charge-reduced protein complexes into subcomplexes, which is also retain native-like structures. The sample stock solution concentrations were measured using a Thermo Scientific NanoDrop 2000C and diluted in the range of 0.7 to 3 µM per complex with or without charge reduction. For T=3 and T=4 hepatitis B virus (HBV) capsids, the concentration was 6 µM per monomer and 4.8 µM per monomer after charge reduction. For the RAS-SOS complex analysis, 3 µM SOS was mixed with 2 µM HRasWT-GTP and immediately introduced into the mass spectrometer via a pulled glass capillary.