ICC-CLASS: isotopically-coded cleavable crosslinking analysis software suite

BMC Bioinformatics. 2010 Jan 28;11:64. doi: 10.1186/1471-2105-11-64.

Abstract

Background: Successful application of crosslinking combined with mass spectrometry for studying proteins and protein complexes requires specifically-designed crosslinking reagents, experimental techniques, and data analysis software. Using isotopically-coded ("heavy and light") versions of the crosslinker and cleavable crosslinking reagents is analytically advantageous for mass spectrometric applications and provides a "handle" that can be used to distinguish crosslinked peptides of different types, and to increase the confidence of the identification of the crosslinks.

Results: Here, we describe a program suite designed for the analysis of mass spectrometric data obtained with isotopically-coded cleavable crosslinkers. The suite contains three programs called: DX, DXDX, and DXMSMS. DX searches the mass spectra for the presence of ion signal doublets resulting from the light and heavy isotopic forms of the isotopically-coded crosslinking reagent used. DXDX searches for possible mass matches between cleaved and uncleaved isotopically-coded crosslinks based on the established chemistry of the cleavage reaction for a given crosslinking reagent. DXMSMS assigns the crosslinks to the known protein sequences, based on the isotopically-coded and un-coded MS/MS fragmentation data of uncleaved and cleaved peptide crosslinks.

Conclusion: The combination of these three programs, which are tailored to the analytical features of the specific isotopically-coded cleavable crosslinking reagents used, represents a powerful software tool for automated high-accuracy peptide crosslink identification. See: http://www.creativemolecules.com/CM_Software.htm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / chemistry*
  • Databases, Protein
  • Isotope Labeling
  • Isotopes / chemistry
  • Mass Spectrometry
  • Peptides / chemistry
  • Proteins / chemistry*
  • Proteomics / methods*
  • Software*

Substances

  • Cross-Linking Reagents
  • Isotopes
  • Peptides
  • Proteins