[PeptideTermMod:Lysine not cleaved at N-term]

smith-chem-wisc / MetaMorpheus

Proteomics search software with integrated calibration, PTM discovery, bottom-up, top-down and LFQ capabilities

MIT License

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[PeptideTermMod:Lysine not cleaved at N-term] #1097

Closed zrolfs closed 5 years ago

zrolfs commented 6 years ago

This seems like a trypsin-specific modification. Should we uncheck it when searching other enzymes? It's popping up in nonspecific searches...

rmillikin commented 6 years ago

Maybe we should have protease-specific mods?

zrolfs commented 6 years ago

Why is this even a thing? Does anybody know?

trishorts commented 6 years ago

GG is a protease specific mod that occurs upon cleaveage of ubiquitin side chains. There are others, and these tags change with other proteases.

zrolfs commented 6 years ago

So lysine not being cleaved is indicative of ubiquitin? I am confused. Isn't this just a missed cleavage that happens to be on the N-terminus?

trishorts commented 6 years ago

No lysine still gets cleaved but there is an addition two amino acid tag hanging off the side

trishorts commented 6 years ago

zrolfs commented 6 years ago

I'm getting it for nonspecific searches where "[PeptideTermMod:Lysine not cleaved at N-term]LWGKQKNK" has the same mass as "KLWGKQKNK" so there doesn't appear to be a GG?

trishorts commented 6 years ago

I don't know what that is. I was talking about protease specific mods. I don't think there should be any for non-specific. The notation you write looks like a uniprot mod. check uniprot ptmlist

rmillikin commented 6 years ago

I removed this mod in #1512 along with a few other ones.

These seem weird to treat these as mods for the above reasons (ambiguity, handling it in 2 places [mods and missed cleavages]) but also because we didn't even check to see if the previous amino acid is a K, to my knowledge...

We could write code for interpreting mass-differences as truncations, unsearched missed cleavages, etc. in an open-mass search. not sure how we should approach it in a notch search, if at all

rmillikin commented 5 years ago

we have protease-specific mods now ("AspN Digested", "Trypsin Digested"). "Trypsin Digested" includes GG on K. I think this issue has already been resolved but maybe I'm misinterpreting...