The Unreasonable Redundancy of Nature's Protein Folds • Hacker News Board

Re: The Unreasonable Redundancy of Nature's Protein Folds

#61

Post by gilleain » Sat, Jun 06, 2026, 7:33 AM UTC

jeejay1 wrote: post #58

gilleain wrote: post #8

Earlier quoted context omitted.

I understood it as metaphor - just that evolutionarily distant sequences can adopt the same (or very similar) folds because there are only a limited number of stable, accessible folds that are possible.

Do you have an example of such sequences in mind? Because I can’t recall any example.

A very reasonable question, that I don't have an immediate concrete answer to!

Apparently I upvoted this question in the past (found it by searching for an answer - no AI, like the good old days)

https://biology.stackexchange.com/questions/2507/are-there-a...

One answer mentions actin and hexokinase. I'm not familiar with the actin fold, but looks like a bab sandwich of some kind.

Another commenter on this page mentioned the 'Rossman fold', another classic, and TIM barrels also occur to me. One caution is that some of these I would consider higher-level patterns - the 'Topology' level of CATH hierarchy.

Naturally, the more high-level (abstract) the fold pattern, the larger the sequence space it covers. It is less interesting to say that a helical bundle (for example) covers a lot of diverse sequences.

Re: The Unreasonable Redundancy of Nature's Protein Folds

#62

Post by DrScientist » Mon, Jun 08, 2026, 8:38 AM UTC

jyounker wrote: post #60

DrScientist wrote: post #59

Earlier quoted context omitted.

> I have a 30 year old book on protein structure on my shelf. One of the primary themes is the recurrence of the same structural motifs in proteins. What you have to be careful about here is that the structure that were available 30 years ago were quite strongly biased by what was experimentally tractable.... ie the recurrence of the same folds is in part related to what crystallised well. > The fact that biologic pr…

> What you have to be careful about here is that the structure that were available 30 years ago were quite strongly biased by what was experimentally tractable.... ie the recurrence of the same folds is in part related to what crystallised well. It was biased in some sense towards those things that could be crystalized, but but at that time we were already seeing the same sorts of recurring motifs with cryo-em which…

No one is arguing reuse is a surprise - there used to be a joke in the early days of protein fold prediction - that if the protein amino acid sequence was a certain length - you just predict TIM barrel and you'd be right.

the question is a separate one - how much of protein universe of folds have already been seen?

Re: The Unreasonable Redundancy of Nature's Protein Folds

#63

Post by jyounker » Mon, Jun 08, 2026, 9:19 PM UTC

DrScientist wrote: post #62

jyounker wrote: post #60

Earlier quoted context omitted.

> What you have to be careful about here is that the structure that were available 30 years ago were quite strongly biased by what was experimentally tractable.... ie the recurrence of the same folds is in part related to what crystallised well. It was biased in some sense towards those things that could be crystalized, but but at that time we were already seeing the same sorts of recurring motifs with cryo-em which…

No one is arguing reuse is a surprise - there used to be a joke in the early days of protein fold prediction - that if the protein amino acid sequence was a certain length - you just predict TIM barrel and you'd be right. the question is a separate one - how much of protein universe of folds have already been seen?

So we're in agreement. The expectation is that biochemistry here on Earth only produces a small proportion of the possible structures.