Wednesday, October 19, 2022

Find those awful miserable stupid labile PTMs with MSFragger Labile!


While it would be amazing if every protein chemical post-translational modification would just stay put when we're gently converting them from solution to ionized gases with

and (for my fellow higher flow HPLC people) plenty of 

Some, maybe the majority of these wimpy PTMs fall right off! 

For a decade I've heard that MaxQuant can make use of diagnostic fragment ions and neutral losses and use it within it's data processing.

And maybe it can, and I'm just too dumb to get it to work. In either case, I don't care, because I CAN MAKE MSFRAGGER DO IT! And you can read about this here. 

If you're a nerd who can't keep looking to see what is in pull-down menus, you might have noticed this showing up in FragPipe 16 or 17 as the ADPr workflow. 

If you're working with ADPr I am truly sorry, because that modification truly fucking sucks. Is it gonna release an ADP? or an AMP for some reason (it might!), it sure is gonna neutral loss 3-6 times in HCD. And those stupid fragments ionize like pure arginine and your search engine is going to assume that you definitely aren't fragmenting peptides. Put some pure ADPribosylated peptides on your LC instrument, put the ADPr on the correct amino acid and tell me how many times a search engine finds it without you manually looking for it. If it happens once it is more times than I've ever seen it happen. 

UNTIL NOW. This weird Java program actually looks like it can do it!  (Low n and something I can't afford to put time into for a while, but this might be a huge step in the right direction.) 

Now, I can't entirely figure out how to modify this to look at another awful PTM, without a calculator and maybe thinking about it really hard, but this might be awesome!

No comments:

Post a Comment