Here we report the first demonstration of near-complete sequence coverage of intact proteins using activated ion-electron transfer dissociation (AI-ETD), a method that leverages concurrent infrared photoactivation to enhance electron-driven dissociation. AI-ETD produces mainly c/z-type product ions and provides comprehensive (77-97%) protein sequence coverage, outperforming HCD, ETD, and EThcD for all proteins investigated. AI-ETD also maintains this performance across precursor ion charge states, mitigating charge-state dependence that limits traditional approaches.
Keywords: activated-ion; electron-transfer dissociation; infrared photons; intact proteins; photoactivation; top-down proteomics.