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Brief Communication

Nature Methods 5, 315–318 (1 April 2008) | doi:10.1038/nmeth.1192

Identification of cross-linked peptides from large sequence databases

Oliver Rinner , Jan Seebacher , Thomas Walzthoeni , Lukas Mueller , Martin Beck , Alexander Schmidt , Markus Mueller & Ruedi Aebersold

We describe a method to identify cross-linked peptides from complex samples and large protein sequence databases by combining isotopically tagged cross-linkers, chromatographic enrichment, targeted proteomics and a new search engine called xQuest. This software reduces the search space by an upstream candidate-peptide search before the recombination step. We showed that xQuest can identify cross-linked peptides from a total Escherichia coli lysate with an unrestricted database search.