CLMSVault: A Software Suite for Protein Cross-Linking Mass-Spectrometry Data Analysis and Visualization

J Proteome Res. 2017 Jul 7;16(7):2645-2652. doi: 10.1021/acs.jproteome.7b00205. Epub 2017 Jun 5.


Protein cross-linking mass spectrometry (CL-MS) enables the sensitive detection of protein interactions and the inference of protein complex topology. The detection of chemical cross-links between protein residues can identify intra- and interprotein contact sites or provide physical constraints for molecular modeling of protein structure. Recent innovations in cross-linker design, sample preparation, mass spectrometry, and software tools have significantly improved CL-MS approaches. Although a number of algorithms now exist for the identification of cross-linked peptides from mass spectral data, a dearth of user-friendly analysis tools represent a practical bottleneck to the broad adoption of the approach. To facilitate the analysis of CL-MS data, we developed CLMSVault, a software suite designed to leverage existing CL-MS algorithms and provide intuitive and flexible tools for cross-platform data interpretation. CLMSVault stores and combines complementary information obtained from different cross-linkers and search algorithms. CLMSVault provides filtering, comparison, and visualization tools to support CL-MS analyses and includes a workflow for label-free quantification of cross-linked peptides. An embedded 3D viewer enables the visualization of quantitative data and the mapping of cross-linked sites onto PDB structural models. We demonstrate the application of CLMSVault for the analysis of a noncovalent Cdc34-ubiquitin protein complex cross-linked under different conditions. CLMSVault is open-source software (available at ), and a live demo is available at .

Keywords: bioinformatics; cross-linker; mass spectrometry; protein interaction; quantification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Binding Sites
  • Cross-Linking Reagents / chemistry*
  • Humans
  • Mass Spectrometry
  • Models, Molecular
  • Peptides / chemistry*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Software*
  • Ubiquitin / chemistry*
  • Ubiquitin-Conjugating Enzymes / chemistry*


  • Cross-Linking Reagents
  • Peptides
  • Ubiquitin
  • CDC34 protein, human
  • Ubiquitin-Conjugating Enzymes