Sunday, March 3, 2019

Intrinsically disordered proteins!

(Figure borrowed from this awesome paper I totally don't get)

Two years ago I was asked by a collaborator (for a paper that was FINALLY accepted this week -- YAY!) to investigate our findings for Intrinsically Disordered Proteins. (IDPs)

I did the right thing and ignored this request completely.

Wanna talk about something that proteomics isn't good at right now? IDPs. Me either. But maybe ignoring a big biological problem that people are increasingly linking to diseases isn't the best idea. And maybe we have tools now?

Should I try to talk about what the problem is first? Sure! That way maybe I'll understand it better. (To clarify -- the original request hasn't actually gone away -- it's simply gotten more urgent).

(BIG Shoutout to Lukasz Kozlowski for making this aweseome open gif!)

This is SUMO or something. You know how all proteins are supposed to work cause they've got 3D structures and things? This gif shows that this protein does have 3D structure in part of it -- but a crazy disordered protein part in others. At first this sounds okay, right? Albert Heck! Who cares? I'm going to reduce and alkylate and digest and that won't matter at all, right?

EXACTLY! That's the point. And part of the problem. We completely trash this information with shotgun proteomics. Heck....I don't know if we retain this information with top-down either...aside from the mass shifts from the free cysteines?!??

See why I ignored this? Okay -- but we have some resources, I guess. I've tried this one --

DisProt is a growing resource. It has information on 800+ proteins of interest now. My profanity laden notes from 2017 suggest that the database was significantly smaller then. Maybe you end up with a list of proteins that make no sense at all to IPA or any other resource -- but it turns out it's an enriched list of disordered proteins? Yeah! That sounds smart as I type it. I plan to not reread it.

Okay -- but what if we take 10 steps backward. What if there was a way to tackle this problem directly? ION MOBILITY TO THE RESCUE!

Did we finally find something that Ion Mobility is critical for?!?!?  (Kidding, I don't really think that every application of IMS could also be solved with 4 minutes of attention to chromatography, but it gets people wound up when you say things like that!)

I'm not even going to read this paper today -- because 1) I don't have IM in house (yet...but maybe this is the reason to get a demo scheduled) and 2) I can't apply this to my original files but if you have someone bugging you about disordered proteins and you haven't added the word as a filter to your spam trigger, maybe you should check it out!

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