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spwa4today at 7:35 AM3 repliesview on HN

This is just repeating the fact that the proteins life actually uses are a very small part of the total possible ones. First, there's no real length limit, but all life's proteins are limited to a few thousand amino acids. Most barely get past hundred.

(note: there are bigger proteins, including ones so big you can see them with the naked eye (e.g. a hair) but they consists of multiple repeats of the same small building block. There are many such building blocks. And the very few exceptions to that are "not really" part of eukaryot cells, but of cell organelles that have their own DNA)

But even if you just take the first 4 amino acids, there's half a million possible combinations. Life uses less than 1000 of those.

In other words: DNA and evolution, even with billions of years to think about it, is really a bit of a beginner when it comes to protein design. Or at least, it is pretty obvious that it's possible to do A LOT better than natural selection.


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gilleaintoday at 7:42 AM

This is about folds, not amino acids - even if you used a larger alphabet of residues, I somehow doubt that you would get many more folds.

Thinking more about the question of protein _length_ - I'm also not convinced that longer proteins (more than say 750aa) would produce more novel folds. Larger proteins tend to be multi-domain; that is, a longer chain will fold into multiple compact domains, each one a separate fold.

I suppose there could be 'megafolds' out there in fold space, beyond 1000aa - like a 12-bladed beta propeller, or a beta-helix with alpha helices on the outside or some other wacky thing. Whether that would substantially increase the numbers of total folds, I doubt, but that is of course a guess.

(ref - https://pmc.ncbi.nlm.nih.gov/articles/PMC10251718/ for protein lengths)

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suncemojetoday at 11:54 AM

> DNA and evolution, even with billions of years to think about it, is really a bit of a beginner when it comes to protein design.

I like how you say evolution is able to think when in reality it's just a mysterious function of variation, selection, and time.

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