Aaaand....in case you were just wondering how you might do NATIVE top down proteomics (what?!?), do I ever have the paper for you!
This paper is quite comprehensive and looks at the fragmentation of something like 150 proteoforms in a bunch of samples to figure out the answer to the questions I expect a lot of people in our field will be asking in they year 2029.
If you wanted to do a comprehensive top down proteome of some cells while leaving the proteins in their fully comformed native state, you may want to use different fragmentation scoring techniques, because they do fragment differently. I'm mostly leaving this here for myself to reference down the road, so I won't get into the data much.
To answer a question no one has asked yet, you need tomorrow's mass spectrometer. This team used a slightly modified high field quadrupole Orbitrap system
that they previously described here.
The minor modifications are that it is capable of MS3 -- can scan up to 20,000 m/z, has a couple ion funnels, and has a quad that can isolate extremely high mass ranges.
This is a great resource today if you're asking questions way more advanced than I am!
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