Algorithms for identifying protein cross-links via tandem mass spectrometry

J Comput Biol. 2001;8(6):571-83. doi: 10.1089/106652701753307494.


Cross-linking technology combined with tandem mass spectrometry (MS-MS) is a powerful method that provides a rapid solution to the discovery of protein-protein interactions and protein structures. We studied the problem of detecting cross-linked peptides and cross-linked amino acids from tandem mass spectral data. Our method consists of two steps: the first step finds two protein subsequences whose mass sum equals a given mass measured from the mass spectrometry; and the second step finds the best cross-linked amino acids in these two peptide sequences that are optimally correlated to a given tandem mass spectrum. We designed fast and space-efficient algorithms for these two steps and implemented and tested them on experimental data of cross-linked hemoglobin proteins. An interchain cross-link between two beta subunits was found in two tandem mass spectra. The length of the cross-linker (7.7 A) is very close to the actual distance (8.18 A) obtained from the molecular structure in PDB.

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Computational Biology
  • Cross-Linking Reagents
  • Data Interpretation, Statistical
  • Hemoglobins / chemistry
  • Humans
  • In Vitro Techniques
  • Mass Spectrometry / methods*
  • Mass Spectrometry / statistics & numerical data
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Probability
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Subunits
  • Proteins / chemistry*
  • Proteome
  • Succinimides


  • Amino Acids
  • Cross-Linking Reagents
  • Hemoglobins
  • Peptide Fragments
  • Protein Subunits
  • Proteins
  • Proteome
  • Succinimides
  • disuccinimidyl glutarate