With proteins, a change of folding is usually indicated by a change in the electrospray charge state distribution: the folded fraction of the population is ionized by the charged residue mechanism, and thus adopt charge states limited by the Rayleigh limit, while the unfolded fraction can be ionized at least partly by chain extrusion, and thus adopts higher charge states. The gas-phase compactness can be probed by ion mobility spectrometry, confirming the correlation between charge state and structure. Even if the gas-phase mobility of low charge states at low internal energy cannot differentiate the molecular interactions involved in two molecular systems, one can increase the internal energy before the ion mobility analyzer and investigate at which voltage the structure unfolds. This type of experiment is often called "collision-induced unfolding" (CIU).