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SporkofVengeance t1_j4uygwb wrote

In which one scientist pretends his insight is novel rather than something practically everyone in the field already knows - including the people who wrote the AF2 and rTTAF code.

He’s aware that Protein Data Bank also holds single, fixed structures, right?

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Moont1de OP t1_j4v8ltr wrote

People outside the field certainly do not know that, Scientific American just had an article about how Alphafold “solved” protein structure prediction.

The PDB holds ensemble data too, by the way

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SporkofVengeance t1_j4vbl33 wrote

The article is in Nature Methods: I expect it is aimed at practitioners.

> The PDB holds ensemble data too, by the way

That's not the point being made: the author wants a distribution of possible conformations (which is perfectly fine). PDB does not have that as it was never designed to. IIRC John Jumper made the point in a couple of lectures where he basically said – because of the way AF2 is trained - it gives you more or less what you'd find in PDB, which can often mean the AF2-predicted conformation assumes the presence of some ligands if that's how the protein was crystallised for X-ray diff or frozen for cryo-EM, but without the ligands being in the predicted structure explicitly.

Molecular dynamics simulations would provide a way to build these distributions (though some of the mods to AF2 and rTTAF do predict some types of conformation change) but you can expect to wait a while for a computer to generate them. Unfortunately, that's currently a geological-time wait. Other forms of ML might bring that down a bit.

The issue with the "solved" quote comes from the CASP guys and should have been reported with some caveats. Prof Moult basically meant solved as far as the CASP contest for single-protein "apo-structure" requirements go. Even then AF2 will generate different results to cryo-EM but results that are most often usable enough to help confirm cryo-EM measurements. So, on balance, people are pretty happy with AF2 as far as it goes and was meant to go. But it's not and was never intended to be a solution to all protein structure questions.

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