alt Hacker NewsThis 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)
Amino acid (sequence) defines the folds.
And really? Just any random sequence gets you a new fold. I mean, it won't be very useful if you pick a random one, but it'll work and be a new one.
I think this is just an artifact of natural selection basing new proteins on existing ones, not an actual useful ("rational" if you can call natural selection rational) selection limit. I don't think that if you designed proteins from first principles you'd see this limitation in your results.