Workflow for cross-linking mass spectrometry relies heavily on effective ion activation methods for the production of informative MS/MS spectra. After optimized incubation of proteins with a cross-linking reagent and proteolytic digestion, four types of peptide products may be created. Cross-linked peptides are subjected to ion activation to generate informative MS/MS spectra.190 Reprinted from Götze, M.; Iacobucci, C.; Ihling, C.H.; Sinz, A. A Simple Cross-Linking/Mass Spectrometry Workflow for Studying System-Wide Protein Interactions, Anal. Chem., 2019, 91, 10236–10244. Copyright 2019 American Chemical Society.