Figure 6 -. Methods that leverage physicochemical properties of native inhibitors for proteome-wide target identification.

a) A class of methods leverage the phenomenon that inhibitor binding tends to stabilize proteins. Proteins are treated with inhibitor, exposed to some destabilizing force, unfolded proteins are removed, and the remainder is quantified against a DMSO control to reveal stabilized proteins, which are inferred to be bound by the inhibitor. b) Precursor-ion scanning methods leverage predictable gas-phase fragmentation behavior of the native inhibitor-peptide adduct. By only sequencing peptides which generate the predicted inhibitor-specific diagnostic ion in initial fragmentation, these methods focus the analytical bandwidth on modified peptides only, thereby mapping proteome-wide targets.