Journal
JOURNAL OF PROTEOME RESEARCH
Volume 22, Issue 1, Pages 101-113Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.2c00500
Keywords
cross-linking mass spectrometry; protein feedback; peptide identification; database search
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In this paper, a comprehensive cross-linking search method called ECL-PF is proposed for cleavable XL-MS data analysis, which can improve the sensitivity of protein-protein interaction detection and protein structure probing.
Improving the sensitivity of protein-protein interaction detection and protein structure probing is a principal challenge in cross-linking mass spectrometry (XL-MS) data analysis. In this paper, we propose an exhaustive cross-linking search method with protein feedback (ECL-PF) for cleavable XL-MS data analysis. ECL-PF adopts an optimized alpha/beta mass detection scheme and establishes protein-peptide association during the identification of cross-linked peptides. Existing major scoring functions can all benefit from the ECL-PF workflow to a great extent. In comparisons using synthetic data sets and hybrid simulated data sets, ECL-PF achieved 3-fold higher sensitivity over standard techniques. In experiments using real data sets, it also identified 65.6% more cross-link spectrum matches and 48.7% more unique cross-links.
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