title: Kojak: efficient analysis of chemically cross-linked protein complexes.
abstract: Protein chemical cross-linking and mass spectrometry enable the analysis of protein-protein interactions and protein topologies; however, complicated cross-linked peptide spectra require specialized algorithms to identify interacting sites. The Kojak cross-linking software application is a new, efficient approach to identify cross-linked peptides, enabling large-scale analysis of protein-protein interactions by chemical cross-linking techniques. The algorithm integrates spectral processing and scoring schemes adopted from traditional database search algorithms and can identify cross-linked peptides using many different chemical cross-linkers with or without heavy isotope labels. Kojak was used to analyze both novel and existing data sets and was compared to existing cross-linking algorithms. The algorithm provided increased cross-link identifications over existing algorithms and, equally importantly, the results in a fraction of computational time. The Kojak algorithm is open-source, cross-platform, and freely available. This software provides both existing and new cross-linking researchers alike an effective way to derive additional cross-link identifications from new or existing data sets. For new users, it provides a simple analytical resource resulting in more cross-link identifications than other methods.
authors: †Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, United States.
authors: Michael R
authors: MR
authors: Hoopmann
authors: ‡Department of Biochemistry, University of Washington, 1705 North East Pacific Street, Seattle, Washington 98195, United States.
authors: Alex
authors: A
authors: Zelter
authors: §Department of Genome Sciences, University of Washington, 3720 15th Avenue North East, Seattle, Washington 98195, United States.
authors: Richard S
authors: RS
authors: Johnson
authors: ‡Department of Biochemistry, University of Washington, 1705 North East Pacific Street, Seattle, Washington 98195, United States.
authors: Michael
authors: M
authors: Riffle
authors: §Department of Genome Sciences, University of Washington, 3720 15th Avenue North East, Seattle, Washington 98195, United States.
authors: Michael J
authors: MJ
authors: MacCoss
authors: ‡Department of Biochemistry, University of Washington, 1705 North East Pacific Street, Seattle, Washington 98195, United States.
authors: Trisha N
authors: TN
authors: Davis
authors: †Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109, United States.
authors: Robert L
authors: RL
authors: Moritz
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D056931:Cryptochromes / Q000737:chemistry; D030562:Databases, Protein; D044783:F-Box Proteins / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping / Q000706:statistics & numerical data*; D040901:Proteomics / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data*; D044786:S-Phase Kinase-Associated Proteins / Q000737:chemistry; D012568:Schizosaccharomyces / Q000737:chemistry; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry; D012984:Software; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: C538966:CRY2 protein, human; D003432:Cross-Linking Reagents; D056931:Cryptochromes; D044783:F-Box Proteins; C519795:FBXL3 protein, human; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D029702:Schizosaccharomyces pombe Proteins
keywords: cross-linking; mass spectrometry; protein structure; proteomics