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[return to "AlphaFold reveals the structure of the protein universe"]
1. COGlor+JD[view] [source] 2022-07-28 15:03:35
>>MindGo+(OP)
Before my comment gets dismissed, I will disclaim I am a professional structural biologist that works in this field every day.

These threads are always the same: lots of comments about protein folding, how amazing DeepMind is, how AlphaFold is a success story, how it has flipped an entire field on it's head, etc. The language from Google is so deceptive about what they've actually done, I think it's actually intentionally disingenuous.

At the end of the day, AlphaFold is amazing homology modeling. I love it, I think it's an awesome application of machine learning, and I use it frequently. But it's doing the same thing we've been doing for 2 decades: pattern matching sequences of proteins with unknown structure to sequences of proteins with known structure, and about 2x as well as we used to be able to.

That's extremely useful, but it's not knowledge of protein folding. It can't predict a fold de novo, it can't predict folds that haven't been seen (EDIT: this is maybe not strictly true, depending on how you slice it), it fails in a number of edge cases (remember, in biology, edge cases are everything) and again, I can't stress this enough, we have no new information on how proteins fold. We know all the information (most of at least) for a proteins final fold is in the sequence. But we don't know much about the in-between.

I like AlphaFold, it's convenient and I use it (although for anything serious or anything interacting with anything else, I still need a real structure), but I feel as though it has been intentionally and deceptively oversold. There are 3-4 other deep learning projects I think have had a much greater impact on my field.

EDIT: See below: https://news.ycombinator.com/item?id=32265662 for information on predicting new folds.

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2. adamsm+BI[view] [source] 2022-07-28 15:26:25
>>COGlor+JD
> it can't predict folds that haven't been seen

This seems strange to me. The entire point of these types of models is to predict things on unseen data. Are you saying Deepmind is completely lying about their model?

Deepmind solved CASP, isn't the entire point of that competition to predict unseen structures?

If AlphaFold doesn't predict anything then what are you using it to do?

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3. COGlor+JJ[view] [source] 2022-07-28 15:30:44
>>adamsm+BI
AlphaFold figures out that my input sequence (which has no structural data) is similar to this other protein that has structural data. Or maybe different parts of different proteins. It does this extremely well.
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4. flobos+LK[view] [source] 2022-07-28 15:35:03
>>COGlor+JJ
This is a gross misrepresentation of the method.
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5. COGlor+6M[view] [source] 2022-07-28 15:40:33
>>flobos+LK
Perhaps you'd care to explain how? AlphaFold does not work on new folds. It ultimately relies on mapping sequence to structure. It does it better than anyone else, and in ways a human probably couldn't, but if you give it a brand new fold with no relation to other folds, it cannot predict it. I routinely areas of extremely low confidence many of my AlphaFold models. I work in organisms that have virtually 0 sequence identity. This is a problem I deal with every day. I wish AlphaFold worked in the way you are suggesting, but it just flat out does not.
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6. dekhn+BS[view] [source] 2022-07-28 16:05:41
>>COGlor+6M
No organisms have virtually 0 sequence identity. That's nonsense. Can you give an example? n Even some random million-year-isolated archae shares the majority of its genes with common bacteria.
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7. COGlor+nY1[view] [source] 2022-07-28 21:41:28
>>dekhn+BS
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