Because the collision cross section (CCS) of a protein is related to its overall shape, the measurement can provide information about various conformations the molecule adopts. A protein’s CCS, which relates its shape to the probability of interacting with gas molecules, is often determined using ion mobility separation in combination with quadrupole-time-of-flight mass spectrometry. Jennifer S. Brodbelt of the University of Texas, Austin, Alexander A. Makarov of Thermo Fisher Scientific, and coworkers now show that they can calculate protein CCS using an Orbitrap mass spectrometer without the need for extra hardware such as an ion mobility cell (Anal. Chem. 2018, DOI: 10.1021/acs.analchem.8b00724). They calculate the CCS from the decay rate of a particular mass-to-charge ratio (m/z) at a particular pressure. Because ions with different CCSs aren’t physically separated, the method provides an average value for all conformations of a given m/z, which means the method is best suited to protein charge states with just a single conformation. The researchers measured the CCS of multiple charge states of three proteins. CCSs obtained with an Orbitrap differed by less than 7% from those measured via ion mobility. Although the new method doesn’t completely replace ion mobility, it might enable more structural biologists to obtain conformational information.