Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

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

deepmind.com

Post reply on HN
Print view View original

491–500 of 683 posts

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

#491

Post by syncsynchalt »

CJefferson wrote: post #23

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.

The article in Science implies that we have independent confirmation of predictions yielding useful results, beyond the challenge itself:

> The organizers even worried DeepMind may have been cheating somehow. So Lupas set a special challenge: a membrane protein from a species of archaea, an ancient group of microbes. For 10 years, his research team tried every trick in the book to get an x-ray crystal structure of the protein. “We couldn’t solve it.”

> But AlphaFold had no trouble. It returned a detailed image of a three-part protein with two long helical arms in the middle. The model enabled Lupas and his colleagues to make sense of their x-ray data; within half an hour, they had fit their experimental results to AlphaFold’s predicted structure. “It’s almost perfect,” Lupas says. “They could not possibly have cheated on this. I don’t know how they do it.”

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

#492

Post by The_rationalist »

ashtonbaker wrote: post #468
The_rationalist wrote: post #435

Earlier quoted context omitted.

but experimental methods have not solved protein folding either. AlphaFold has'nt solved protein folding but I can't wait to see their progress for ALphaFold 3. What would be informatively useful would be to know how much accuracy is needed on average for drug engineers, I'd say that 99% is more likely to be the minimum to make solid inferences

> but experimental methods have not solved protein folding either. I might be missing something here, but isn't "experimental methods" just shorthand for "our best knowledge of a protein's structure, obtained via NMR or X-ray crystallography"? In that case, I'm not sure what "solving" protein folding even means - literally zero mean error? We can't know/solve anything beyond our best knowledge, that's tautological. >…

It's pretty clear what solving means, it means to have an exact representation of the 3D structure. Our partial knowledge obtained from such techniques is what it is, partial. We need new metrology that increase the observability accuracy and completeness OR better deterministic models from sequences.

"We can't know/solve anything beyond our best knowledge, that's tautological." yes it is indeed tautological if you assume that experimental methods can't get better then guess what? It follows that they can't get better!

"what are you basing this on?" on nothing solid, that's why I say it would be interesting. 99% is a non negligible error rate given that proteins have generally a not very high atom count and they the protein will be produced an enormous amount of time, then the 1% error progagate and can a priori easily break the system. But this guess is not solid as I'm not an expert. 99% accuracy for simple (low atom count) proteins is a sensitive error and could be negligible for very high atom count proteins.

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

#493

Post by flobosg »

shawnz wrote: post #79
xbmcuser wrote: post #47

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

De novo design of protein logic gates: https://science.sciencemag.org/content/368/6486/78

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

#494

Post by 14 »

pmastela wrote: post #371
ramraj07 wrote: post #236

Earlier quoted context omitted.

The most amazing part: > The organizers even worried DeepMind may have been cheating somehow. So Lupas set a special challenge: a membrane protein from a species of archaea, an ancient group of microbes. For 10 years, his research team tried every trick in the book to get an x-ray crystal structure of the protein. “We couldn’t solve it.” > But AlphaFold had no trouble. It returned a detailed image of a three-part pro…

Like the old Arthur C. Clark quote goes: “Any sufficiently advanced technology is indistinguishable from magic” -- unless it might be cheating in which case throw them a curve ball. Kudos to the DeepMind team for making magic happen.

I am happy you mention this. I was reading the article and thinking “wow the amount of scientific knowledge these guys need to know to understand what they are doing is way beyond me”. I work in health care and I always talk to clients about all the cool things they witnessed in their life. Cell phones, TVs, microwaves are some obvious ones I like to talk about. I sit and wonder what are the things my generation will get to look back on and say “I was alive when that happened”. I guess for many of us we will talk about how the internet was vs what it surely will be in the future, a shell of its initial glory.

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

#495

Post by nathancahill »

kovek wrote: post #470
dang wrote: post #464

All: there are multiple pages of comments; if you're curious to read them, click More at the bottom of the page, or like this: https://news.ycombinator.com/item?id=25253488&p=2 We changed the URL from https://predictioncenter.org/casp14/zscores_final.cgi to the blog post, which has more background info.

I've seen you mention this [More] comment a few times now. I like it, though what if you change the design of the More functionality?

Also, what do the traffic stats look like for the second/third pages of big threads like this one? Pretty steep falloff?

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

#496

Post by _RPL5_ »

dalke wrote: post #403
_RPL5_ wrote: post #377

Earlier quoted context omitted.

The industry process will not change. You still need industrial biologists to generate and validate AphaFold structures, interpret the results as part of the bigger picture, and to finally design the drugs. And, then, of course you still need to validate the drugs in experimental systems (first the test tube, then mice, then humans). So your second guess is correct - one of the steps is much cheaper now, which margin…

> "armies of students who routinely spend 4-6 years of their PhD trying to solve a structure of a single protein" Back in the 1990s, when I worked on structure data, I remember that at least some crystallizations were easy enough they could be done as a rotation project. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287266/ suggests that life is now a lot easier than the 1990s. Quoting the abstract: > Macromolecular…

You aren't wrong. I got caught up making the comparison between structural biologists and taxi drivers being ran out of business by AI, so I ended up exaggerating the work load that's addressed by AlphaFold. I should been more precise.

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

#497

Post by codingslave »

softwaredoug wrote: post #487
cs702 wrote: post #118

Two years ago, after DeepMind submitted its first set of predictions to CASP (Critical Assessment of protein Structure Prediction), Mohammed AlQuraishi, an expert in the field, asked, "What just happened?" https://moalquraishi.wordpress.com/2018/12/09/alphafold-casp... Now that the problem of static protein structure prediction has been solved (prediction errors are below the threshold that is considered acceptable i…

> I don’t think we would do ourselves a service by not recognizing that what just happened presents a serious indictment of academic science. Much like other fields, I do begin to question the academic structure to making advances. It appears something is rotten in the state of academia. Oddly it's academia doing incremental improvements to existing methods but industry making novel leaps and bounds... The other majo…

Academia keeps employing people who have done well in classes and within fine bounds. Its a careerist track. Industry cares about results, its more meritocratic

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

#498

Post by dekhn »

ramraj07 wrote: post #236
mncharity wrote: post #64

Additional commentary in Science: https://www.sciencemag.org/news/2020/11/game-has-changed-ai-... (submitted by furcyd : https://news.ycombinator.com/item?id=25254888 ).

The most amazing part: > The organizers even worried DeepMind may have been cheating somehow. So Lupas set a special challenge: a membrane protein from a species of archaea, an ancient group of microbes. For 10 years, his research team tried every trick in the book to get an x-ray crystal structure of the protein. “We couldn’t solve it.” > But AlphaFold had no trouble. It returned a detailed image of a three-part pro…

If I interpret this properly, they're saying they used the DM prediction (not an actual model, just a prediction) to do molecular replacement (https://en.wikipedia.org/wiki/Molecular_replacement) which sounds pretty audacious. I see it recently made it into the literature: https://journals.iucr.org/m/issues/2020/06/00/mf5047/index.h...

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

#499

Post by bosswipe »

elcritch wrote: post #270
beowulfey wrote: post #249

Earlier quoted context omitted.

I mean, credit where credit is due. Google employs some of the greatest names in artificial intelligence and the DeepMind team had a huge chunk of them working on this problem. While the resources may have been available, I don’t think any other single institution had the level of brain power.

It also makes one reconsider the notion that monopolies are entirely bad. This essentially appears to be a vanity project for Google. Though of course they'll benefit from it in many ways, but it's not like they're doing this as the core product of their service. It's a pretty awesome achievement.

Imagine we lived in a culture that did not believe "government is always bad at everything". Government could then pay Google-level salaries and provide Google-level resources to the top minds in the world and give them free rein to tackle problems like this. It's worked in the past, such as Manhattan project or moon landing. But I don't think it's doable nowadays because of the anti-government political culture. Even when government is fully funding things these days the work has to be farmed out to private interests.
Post reply on HN