Xilmass: A New Approach toward the Identification of Cross-Linked Peptides

Anal Chem. 2016 Oct 18;88(20):9949-9957. doi: 10.1021/acs.analchem.6b01585. Epub 2016 Sep 28.

Abstract

Chemical cross-linking coupled with mass spectrometry plays an important role in unravelling protein interactions, especially weak and transient ones. Moreover, cross-linking complements several structural determination approaches such as cryo-EM. Although several computational approaches are available for the annotation of spectra obtained from cross-linked peptides, there remains room for improvement. Here, we present Xilmass, a novel algorithm to identify cross-linked peptides that introduces two new concepts: (i) the cross-linked peptides are represented in the search database such that the cross-linking sites are explicitly encoded, and (ii) the scoring function derived from the Andromeda algorithm was adapted to score against a theoretical tandem mass spectrometry (MS/MS) spectrum that contains the peaks from all possible fragment ions of a cross-linked peptide pair. The performance of Xilmass was evaluated against the recently published Kojak and the popular pLink algorithms on a calmodulin-plectin complex data set, as well as three additional, published data sets. The results show that Xilmass typically had the highest number of identified distinct cross-linked sites and also the highest number of predicted cross-linked sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Calmodulin / analysis*
  • Calmodulin / chemistry
  • Cross-Linking Reagents / chemistry
  • Databases, Protein
  • Humans
  • Plectin / analysis*
  • Plectin / chemistry
  • Succinimides / chemistry
  • Tandem Mass Spectrometry

Substances

  • Calmodulin
  • Cross-Linking Reagents
  • Plectin
  • Succinimides
  • disuccinimidyl suberate