de novo protein sequencing by mass spectrometry MS/MS PSI-MI de novo protein sequence MI:0032 The strategy to determine the complete amino acid sequence of a protein by mass spectrometry relies on the generation of a nested set of fragments differing by one amino acid. This reveals the identity of the residue that has been removed at each degradation step by measuring the mass difference of fragments differing of one residue. Peptide fragments can be obtained by protease treatment combined with the fragmentation promoted by collision (or other methods) within a tandem mass spectrometer. This approach can be carried out with LC MS/MS (Liquid Chromatography Tandem Mass Spectrometry), nanoESI MS/MS (nanoElectrospray Ionisation tandem mass spectrometry), or FTMS (Fourier Transform mass spectrometry) instruments. protein sequence identification Identification by mass spectrometry experimental feature detection