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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

#151

Post by whatshisface »

fabian2k wrote: post #117
derefr wrote: post #89

Earlier quoted context omitted.

170k is "a few" compared to 180 million (i.e. the size of the PDB as soon as someone runs AlphaFold over everything in the UniProt.) > In most cases the proteins were determined to be interesting by other experiments, and then people decided to try and solve their structure. Yes, that's what we're doing right now , because structure is not a useful predictor, because we don't have structure available in advance of st…

Determining what a protein structure does might be even harder than folding. Right now we can't really do that ab initio, you have determine the activity in the lab and then look at the structure. And that allows you to potentially identify this motif in other proteins. If someone produces an AI that you give a sequence and it tells you what the protein does exactly, I'd be extremely impressed. I don't see that happe…

My understanding of this is not perfect, but wouldn't answering the "actually does" question require a full biomolecular model of the cell, or even the whole organism? If so I see what you mean. I suppose that it might be possible to get around this by improving the theory of catalysts so that you could look at a site and say, "oh, this will act in such a way..." Dynamic quantum simulation of a few atoms at the active site is hardly easy but a far sight easier than the other.

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

#152

Post by 6gvONxR4sf7o »

hans1729 wrote: post #140
EgoIncarnate wrote: post #88

"AlphaFold achieves a median score of 87.0 GDT". Game changing, and a huge improvement, but not 100% solved. Also this is for static folding. Dynamic folding and interaction is a much harder problem. Those need to be tackled too before I would consider protein folding 'solved'.

>Those need to be tackled too before I would consider protein folding 'solved' Semantics. From a systemtheoretical point of view, dynamic folding is an abstraction of static folding; solve (i.e. understand the underlying mechanisms) static folding and you can start progressing on dynamic folding, building up on your previously achieved solution. Wether it's solved or not depends on wether you mean `general folding` o…

Solve could mean understanding the underlying mechanism, but in this case, I don’t think that’s how they did it.

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

#154

Post by joshuamorton »

ClumsyPilot wrote: post #134
jhrmnn wrote: post #115

Earlier quoted context omitted.

By this metric, nothing has been ever solved in natural sciences. So this is not a useful metric.

Has it not? Neuton's laws of motion and Ohm's law are pretty om point

Not when you introduce quantum effects.

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

#156

Post by caymanjim »

ClumsyPilot wrote: post #134
jhrmnn wrote: post #115

Earlier quoted context omitted.

By this metric, nothing has been ever solved in natural sciences. So this is not a useful metric.

Has it not? Neuton's laws of motion and Ohm's law are pretty om point

Newton's laws of motion were not a complete solution, as they didn't account for relativity.

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

#157

Post by [deleted] »

partingshots wrote: post #3

I continue to be impressed by how quickly DeepMind has managed to progress in such a short time. CASP13 was a shocker to all of us I think, but many were skeptical as to the longevity of the performance DeepMind was able to achieve. I believe with CASP14 rankings now released, it's safe to say that they've proven themselves. Congratulations to the team! This work will have far reaching impacts, and I hope that you co…

[deleted]

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

#158

Post by flobosg »

entropicdrifter wrote: post #81
fabian2k wrote: post #59

Earlier quoted context omitted.

"A few" does appear quite dismissive of the enormous amounts of effort in structural biology so far. There are more than 170,000 structures in the PDB right now. To determine potential targets for drugs we have to understand what the proteins do. Having the structure is not really enough for that, it doesn't tell you the purpose of the protein (though it certainly can give you some hints). In most cases the proteins…

170,000 is three orders of magnitude less than the number of recorded protein sequences. I don't think it's dismissive to describe that as comparatively few.

Structure is much, much more conserved than sequence. In other words, protein sequences with low sequence identity can fold similarly due to the physical constraints that guide protein folding.

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

#159

Post by allenz »

jeffbee wrote: post #53

Pretty interesting that they only used about $15k worth of resources (retail price) to achieve this. It's not a technique that would have been out of reach for other organizations based only on not being able to afford the compute.

That’s only for the final model. To find it, they’d need to run 1,000 experiments, trying many high-level approaches, many architectures for each component, hyperparameter search, and multiple seeds. Large machine learning projects need $10M in capital.

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

#160

Post by jjk166 »

Rochus wrote: post #144
jjk166 wrote: post #126

Earlier quoted context omitted.

The forward folding problem lets you determine structures from a known genetic sequence. So for example you could very quickly sequence the genome of a virus and figure out how it worked much faster than current methods allow. The reverse folding problem lets you specify a structure and then make a genetic sequence to produce it. For example you could look at this virus to see how it infects its host, then design a c…

The set of all proteins which can potentially be expressed in an organism is known. Now maybe we also get decent (static) structure information for these. But the interaction of a virus with the host cell is much more complex. There is much more than just an amino acid sequence involved. And these parts are all moving, so a static picture as we now can create faster than before does not contain all the information ne…

Precisely why I referred to it as a different and harder problem
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