De Novo Peptide Sequencing Using Exhaustive Enumeration of Peptide Composition

Matthew T. Olson, Jonathan A. Epstein, Alfred L. Yergey

Research output: Contribution to journalArticlepeer-review


We introduce the use of a peptide composition lookup table indexed by residual mass and number of amino acids for de novo sequencing of polypeptides. Polypeptides of 1600 Daltons (Da) or more can be sequenced effectively through exhaustive compositional analysis of MS/MS spectra obtained by unimolecular decomposition (without CID) in a MALDI TOF/TOF despite a fragment mass accuracy of 50 mDa. Peaks are referenced against the lookup table to obtain a complete profile of amino acid combinations, and combinations are assembled into series of increasing length. Concatenating the differences between successive entries in compositional series yields peptide sequences that can be scored and ranked according to signal intensity. While the current work involves measurements acquired on MALDI TOF-TOF, such general treatment of the data anticipates extension to other types of mass analyzers.

Original languageEnglish (US)
Pages (from-to)1041-1049
Number of pages9
JournalJournal of the American Society for Mass Spectrometry
Issue number8
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

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