We investigated the dynamics of protein kinase DNA dependent protein kinase catalytic subunit (DNA-PKcs) through hydrogen deuterium exchange mass spectrometry. Over 1100 peptides could be monitored throughout the kinetics experiment, showing the utility of our nanospray HX-MS configuration for ultra-large proteins such as DNA-PKcs. To match the structurally unassigned helices to sequence from the large disordered regions of DNA-PKcs (a.a 2577-2773), we used integrative modelling. Two sequence assignments were possible. The cluster of models with the helix assignment towards the N-terminal side was favored by reduced kinetics of exchange as measured by HX-MS.