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Comment by spwa4

2 days ago

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.

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spwa4

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gilleain  2 days ago

A random sequence may not fold at all! I seem to remember a paper that tried this, creating a bunch of random proteins, and checking how much structure they had - I think they were helical bundles, but don't quote me.

The nice thing about stable folds, is that 'nearby' sequences in sequence space - as in, point mutations - are the same fold. If each sequence had a completely different fold, then mutation would be much more destructive. Surprisingly, however, sequences that are far apart in sequence space can also adopt the same fold (convergent evolution).

  • flobosg  1 day ago

    This reminds me of structural studies in proteins encoded by de novo genes in eukaryotes. They are usually either intrinsically disordered or adopt a molten-globule-like state.