Instrumentation and experiments. Experiments were conducted on a timsTOF Pro (TIMS-Q-TOF) (Bruker Inc., Billerica, MA), modified for the research presented here. A 385 kHz RF frequency quadrupole driver was installed to extend the quadrupole isolation range from 3,000 m/z with a commercial 1 MHz RF frequency quadrupole driver to 17,000 m/z. Here, we used ESI Tuning Mix and protein complexes (chargereduced streptavidin, C-reactive protein, pyruvate kinase, and glutamate dehydrogenase) for quadrupole calibration up to 12,000 m/z. With the described modifications, the quadrupole can isolate a single charge state at 16,200 m/z with an isolation width of 25 m/z (Figure ). Table shows the default instrument parameters of the commercial instrument for analyzing small molecules in column two and the recommended settings for proteins/protein complexes in columns 3-5.