Kojak: efficient analysis of chemically cross-linked protein complexes

J Proteome Res. 2015 May 1;14(5):2190-8. doi: 10.1021/pr501321h. Epub 2015 Apr 15.

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.

Keywords: cross-linking; mass spectrometry; protein structure; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Cross-Linking Reagents / chemistry
  • Cryptochromes / chemistry
  • Databases, Protein
  • F-Box Proteins / chemistry
  • Humans
  • Molecular Sequence Data
  • Protein Interaction Mapping / statistics & numerical data*
  • Proteomics / economics
  • Proteomics / methods
  • Proteomics / statistics & numerical data*
  • S-Phase Kinase-Associated Proteins / chemistry
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces pombe Proteins / chemistry
  • Software*
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • CRY2 protein, human
  • Cross-Linking Reagents
  • Cryptochromes
  • F-Box Proteins
  • FBXL3 protein, human
  • S-Phase Kinase-Associated Proteins
  • SKP1 protein, human
  • Schizosaccharomyces pombe Proteins