Mango: A General Tool for Collision Induced Dissociation-Cleavable Cross-Linked Peptide Identification

Chemical cross-linking combined with
mass spectrometry provides
a method to study protein structures and interactions. The introduction
of cleavable bonds in a cross-linker provides an avenue to decouple
released peptide masses from their precursor species, greatly simplifying
the downstream search, allowing for whole proteome investigations
to be performed. Typically, these experiments have been challenging
to carry out, often utilizing nonstandard methods to fully identify
cross-linked peptides. Mango is an open source software tool that
extracts precursor masses from chimeric spectra generated using cleavable
cross-linkers, greatly simplifying the downstream search. As it is
designed to work with chimeric spectra, Mango can be used on traditional
high-resolution tandem mass spectrometry (MS/MS) capable mass spectrometers
without the need for additional modifications. When paired with a
traditional proteomics search engine, Mango can be used to identify
several thousand cross-linked peptide pairs searching against the
entire Escherichia coli proteome. Mango provides
an avenue to perform whole proteome cross-linking experiments without
specialized instrumentation or access to nonstandard methods.