title: Database search algorithm for identification of intact cross-links in proteins and peptides using tandem mass spectrometry.
abstract: A new database search algorithm has been developed for identification of intact cross-links in proteins and peptides from tandem mass spectrometric data. Using this algorithm, intact cross-links can be identified and characterized in proteins and peptides with high confidence. The algorithm was tested using BS(3) (bis[sulfosuccinimidyl] suberate) cross-linked Cytochrome C. Five cross-links were identified and verified for spatial plausibility by comparison with its three-dimensional structure at optimized experimental conditions. The distributions of statistical scores for true and false positives and receiver operating characteristic analysis indicate that the algorithm is capable of discriminating true positive cross-linked peptide-spectrum matches from false ones. It has also been demonstrated that the MassMatrix database search engine is capable of searching for intact cross-links in complex Escherichia coli proteome samples cross-linked by BS(3). The new algorithm in MassMatrix offers an additional approach for the discovery of cross-links in proteins and peptides from tandem mass spectrometric data.
authors.affiliation: Proteomics and Informatics Services Facility, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois 60612, USA. huaxu@uic.edu
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.forename: Liwen
authors.initials: L
authors.lastname: Zhang
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
authors.forename: Michael A
authors.initials: MA
authors.lastname: Freitas
mesh_terms: D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D057225:Data Mining / Q000379:methods*; D030562:Databases, Protein; D006736:Horses; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D013388:Succinimides / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014357:Trypsin
chemical_list: D003432:Cross-Linking Reagents; D010446:Peptide Fragments; D011506:Proteins; D013388:Succinimides; D045304:Cytochromes c; C035760:bis(sulfosuccinimidyl)suberate; D014357:Trypsin
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