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AlphaFold: a solution to a 50-year-old grand challenge in biology

deepmind.com

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Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#71
post #37

Earlier quoted context omitted.

Protein folding is a big and important problem, so this is certainly big news if it works as well as it seems. But I wouldn't assume that this changes everything, we can already determine how proteins fold by experimental work. The disadvantage is that this is a lot of work, though the methods there also improved a lot. One question is how robust the predictions are that DeepMind produces. I would also assume that ri…

We can already determine how a few proteins (170k — which sounds like a lot, but which is only 0.09% of all currently-catalogued protein sequences) fold by experimental work. What an accurate model of protein folding allows us to do, is to take our big database of DNA, predict protein foldings for all of it, and then stand up a search index for this database, keying each amino-acid "row" by the "words" of its predict…

Considering that this system "uses approximately 128 TPUv3 cores (roughly equivalent to ~100-200 GPUs) run over a few weeks" to determine a single protein structure, making predictions for all proteins encoded in a human genome seems impractical at this stage. With luck, this advance will help lead to discovery and definition of new folding rules and optimizations that will make protein folding predictions for the whole human genome more tractable.

Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#72

What are the immediate real-world applications of this? Just asking, because I have very little knowledge in this area.

For-profit corporations that value protein engineering will beat a path to DeepMind's door ASAP, like pharmas.

Protein conformation prediction is essential when engineering new small-molecule drug compounds that must 'dock' with the specific proteins that regulate disease. Knowing how to create a protein with the precise shape to become biologically active has soaked up a lot of R&D funding toward pie-in-the-sky techniques that promise to advance that agenda (like quantum or DNA computing).

If this method works as DeepMind says, it will immediately be adopted by every pharma to assess and tweak the shape of candidate proteins.

Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#75

What are the immediate real-world applications of this? Just asking, because I have very little knowledge in this area.

Given the DNA code for one of the "machines" that run cells, we can generate an atomic model of that machine. This means we can "compile" (one part of) the DNA code. It was already possible, but so slow that entire datacenters would spend months calculating this for a single protein and even then we can't use them on the really complex ones at all, necessitating things like neutron spectroscopy which are totally insa…

This is about proteins, not DNA.

Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#78

Been out of the field for a while, could someone currently in it qualify these results? Hyperbolic title notwithstanding, they approach 90% median free modeling accuracy. The "other 90%" still remains to be solved...

I don't think anyone on HN is going to have more authority to qualify the results than the independent experts quoted in the linked article. Among whom are numbered a Nobel laureate, the president of the group that designs the tests of protein folding systems, and the former CEO of Genentech+current CEO of Calico.

Art's a smart guy and I have a lot of respect for his biological intuition, but his understanding of computational biology is very limited.

Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#79

This is a lot bigger than people are assuming if protein folding can be done quickly and cheaply it will trickle down to a lot more than medicine. It is going to advance bio fuels, food production and a lot more.

Imagine protein computers or protein metamaterials

Re: AlphaFold: a solution to a 50-year-old grand challenge in biology

#80

Has anyone got any good other references for this? After some of the dodgy experiments related to alpha zero (comparing to purposefully degraded chess systems), I'd love to see some independent analysis.

CASP is that independent analysis...
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