Cross-linking reagents are such a great idea for studying lots of things. But they can be some cumbersome to work with that a lot of groups just ignore them altogether. Sven Giese et al., thought it would be worth it to take a deeper look at high resolution CID fragmentation nearly a thousand known cross-linked species to see if we just aren't looking for the correct fragment ion species with our typical techniques.
Turns out that might be exactly what is happening. Taking what they learned from the known peptide high resolution study, they were able to boost the identification rate of their unknowns by 9x over traditional search engines.
Worth noting that they did a lot of this with custom coding in Python, so these tools might not immediately be accessible to all of us, but I bet some smart coder could integrate this info into some user-friendlier tool!
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