title: Algorithms for identifying protein cross-links via tandem mass spectrometry.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Southern California, Los Angeles, CA 90089, USA. tingchen@hto.usc.edu
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: J D
authors.initials: JD
authors.lastname: Jaffe
authors.forename: G M
authors.initials: GM
authors.lastname: Church
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D019295:Computational Biology; D003432:Cross-Linking Reagents; D003627:Data Interpretation, Statistical; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011336:Probability; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry*; D020543:Proteome; D013388:Succinimides
chemical_list: D000596:Amino Acids; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D010446:Peptide Fragments; D021122:Protein Subunits; D011506:Proteins; D020543:Proteome; D013388:Succinimides; C096464:disuccinimidyl glutarate