[jyounker]

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. The fact that biologic proteins use the same patterns for different functions isn't new information.

The result also fits in with the rest of biochemistry. While there are a vast variety of interesting chemicals in living things, and they do all sorts of amazing stuff, there are really only a handful of classes of chemicals.

The variety of classes of chemicals that can exist dwarfs what gets used in biochemistry. Why would we expect structure to be different?

We're in agreement though, that it would be interesting to understand what the constraints are.

[DrScientist]

> 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 proteins use the same patterns for different functions isn't new information.

Absolutely. The question is how big is the space - and what percentage of it have we already seen.

> The variety of classes of chemicals that can exist dwarfs what gets used in biochemistry. Why would we expect structure to be different?

Depends on whether the structure universe is specifically a small almost fully explored subset for that very reason. ie biology has choosen a structural subset of possible chemical space by choosing a tiny subset of chemistry.

[jyounker]

> 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 is much less restrictive in the required preparations. (Purify it and flash freeze it.)

In the last 30 years there's nothing that has overturned the recurrence of motifs in protein structure. It's just become more and more established.

This paper confirms that.

The methods they're using are interesting, but the fundamental result isn't surprising.

[DrScientist]

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?

[jyounker]

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