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Chemistry Nobel: Computational protein design and protein structure prediction
- KasianFranks 2y agoAnd, at the heart of AlphaFold2 is the language model, the tip of the spear in AI today. 'Language' can come in many forms e.g. a protein or amino acid sequence.
- paulwetzel 2y agoWhile I am skeptical about yesterdays award in physics, these are totally deserved and spot on. There are few approaches that will accelerate the field of drug development and chemistry as a whole in a way that the works of these three people will. Congratulations!
- ackbar03 2y agoI was just wondering when they were going to award the alphafold2 guys the nobel after after seeing Hinton win the physics one. 100% agree, all three of them totally deserve this one. Baker's lab is pretty much keeping Deepmind in check at this point and ensuring open source research is keeping up. Hats off
- theGnuMe 2y agoBaker has been in the protein folding game for a long time and was the leader before Alphafold came in... His generative paper came out what last year (2023)? I mean this is a fast award cycle.
- divbzero 2y agoDavid Baker’s RoseTTAFold was first released in 2021. [1]: https://www.science.org/doi/10.1126/science.abj8754 https://www.science.org/doi/10.1126/science.abj8754 [2]: https://cen.acs.org/analytical-chemistry/structural-biology/Accurate-protein-structure-prediction-AI/99/i26 https://cen.acs.org/analytical-chemistry/structural-biology/...
- tomp 2y agoAre they? What did Demis do?
- world2vec 2y agoHe's founder and CEO of the AI lab that build Alphafold?
- devilzhong 2y agoThen maybe Sergey and Larry should also get the prize since they founded Google, which owns Deepmind?
- world2vec 2y agoThey were not equal contributors to the seminal paper that got the prize. From another post in this thread: "These authors contributed equally: John Jumper, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Olaf Ronneberger, Kathryn Tunyasuvunakool, Russ Bates, Augustin Žídek, Anna Potapenko, Alex Bridgland, Clemens Meyer, Simon A. A. Kohl, Andrew J. Ballard, Andrew Cowie, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Demis Hassabis"
- theGnuMe 2y agoThey bought it and it runs autonomously (or did mostly)
- onursurme 2y agoHe writes software in different areas, so he has the potential to get a Nobel prize in any area soon.
- seydor 2y agodidn't he lead early successes in RL which popularized it and culminated in protein prediction?
- cowsandmilk 2y agoBoth Rosetta and DeepMind have made contributions outside of protein structure prediction that are far more important for drug discovery.
- mihaaly 2y agoThe physics prize should have went to Elon Musk! Also I really hope the Nobel Prize of Economics goes to Bill Gates! He facilitated sooo much advances by releasing Excel that this must be recognized! And based on this year's announcements so far I am not sure that my sarcastic comments should be taken as a joke!
- theGnuMe 2y agoExcept Excel has introduced way to many bugs and how many people has it killed?
- trott 2y ago> There are few approaches that will accelerate the field of drug development and chemistry as a whole in a way that the works of these three people will. As the author of one such approach, I'm skeptical. AlphaFold 2 just predicts protein structures. The thing about proteins is that they are often related to each other. If you are trying to predict the structure of a naturally occurring protein, chances are that there are related ones in the dataset of known 3D structures. This makes it much easier for ML. You are (roughly speaking) training on the test set. However, for drug design, which is what AlphaFold 3 targets, you need to do well on actually novel inputs. It's a completely different use case. More here: https://olegtrott.substack.com/p/are-alphafolds-new-results-a-miracle https://olegtrott.substack.com/p/are-alphafolds-new-results-...
- jhbadger 2y agoProtein structures are similar to each other because of evolution (protein families exist because of shared ancestry of protein coding genes). It's not a weird coincidence that helps ML; it's inherent in the problem. Same with drug design -- very, very, few drugs are "novel" as opposed to being analogues of something naturally in the body.
- svara 2y agoThey're referring to the structure of the protein when a drug is bound, that's what's novel. Novel as in, you can't think of it as "just" interpolation between known structures of evolutionarily related proteins. That said I'm not sure that's entirely fair, since Alphafold does, as far as I know, work for predicting structures that are far away from structures that have previously been measured. You're quite wrong about small molecule drug structures. Historically that has been the case but these days many lead structures are made by combinatorial chemistry and are not derived from natural products.
- jhbadger 2y agoBut even drugs made by combinatorial chemistry still generally end up being analogues of natural products even if they aren't derived from them. As Leslie Orgel said "Evolution is cleverer than you are"; chemists are unlikely to discover a mechanism of action that millions of years of evolution hasn't already found.
- refurb 2y agoAs someone in the drug discovery business I’m skeptical as I’ve seen many such “advances” flop. I remember when computer aided drug design first came out (and several “quantum jumps” along the way). While useful they failed often at the most important cases. New drugs tend to be developed in spaces we know very little about. Thus there is nothing useful for AI to be trained on. Nothing quite like hearing from the computational scientist “if you make this one change it will improve binding by 1000x”. Then spending 3 weeks making it to find out it actually binds worse.
- hackernewds 2y agoWell deserved! My only qualm is it should've been awarded to the team, vs individuals It needed Oriol as well doing IC work
- nialv7 2y agoPeople joked maybe the Nobel committee is holding some AI stocks. Now I start to wonder if that is true...
- ramraj07 2y agoThis is legitimately deserved though.
- astrange 2y agoMaybe the transformers authors will win Literature.
- deleted 2y ago[deleted]
- joelthelion 2y agoThey are indeed the largest contributors of new books published on Amazon...
- Ekaros 2y agoI would actually not even be mad. After all it is fundamental change in production of literature works.
- InkCanon 2y agoNext up: The Nobel peace prize is awarded to ChatGPT, because virtually all communiques and peace treaties will be generated by lazy lawyers.
- gizajob 2y agoWhoa. Happy for Demis today. Amazing achievement.
- rswail 2y agoThe physics prize was a stretch of the definition of the word "physics", but this one is purely about chemistry.
- gilleain 2y agoDavid Baker (and colleagues) have always done good work. I guess google have done some things also. (lol - one of the PDF attachments to that page is 'Illustration: A string of amino acids' : actually it's a bit better than the title implies :). Actually, Figure 2 - "How does AlfaFold2 Work?" is impressive to fit that on one page. Nice.
- exmadscientist 2y agoIt is well known around here that Baker does very, very little of the work. He is extremely good at putting his name on his students' work though (this is par for the course in academia)... and removing theirs (this is the bad part). At least he bribes them with lots of happy hours!
- stanford_labrat 2y agousername...checks out
- alexmolas 2y agoAnd the literature Nobel will go for ChatGPT
- andy_ppp 2y agoEventually, potentially 10 years away if we continue to see improvements.
- famouswaffles 2y agoYes eventually GPT itself may be capable of winning a Nobel off its own writing but before then..the authors of the Transformer might win one ? Certainly seems a lot more plausible now.
- throw310822 2y agoHaha, wrote the exact same.
- sikimiki 2y agoWell deserved! Especially for Alphafold. It is the most impactful invention in structural biology this century along with Cryo-EM.
- onursurme 2y agoIt doesn't deserve a Chemistry Nobel prize. It deserves a prize about computers.
- seydor 2y agophysiology&medicine more likely
- Mklomoto 2y agoSo the Nobel commite was wrong to decide this because you think otherwise? Interesting. Any more indepth analys about this? Btw. you don't just build AlphaFold by doing only 'computers'. Take a look at any good docmentary about it and you will see that they do discuss chemistry on a deep level
- onursurme 2y agoDeepmind isn't a chemistry company. Demiss Hassabis isn't a chemist. A tool they developed in their area may turn out to be useful in Chemistry. They may spend some relatively short time and effort to apply their tool to Chemistry. They can do the same thing in many areas in every few years and collect all the Nobel's in many areas. That effort is worth for a prize but the context is different. It is possible that some committee members might have raised this same concern in their discussions. relatively short : in comparison to real chemists, whose work is the basis for this development. This is my first interaction in Hackernews, and I was expecting a more polite discussion. I just expressed my idea. You could ask for my explanations.
- Mklomoto 2y agoYou didn't start a discussion with a good argument from begin with though. And i personally really think if people from a different field, jump into a new field and revolutionize it, a nobel price is not a bad thing to appreciate this effort.
- proto-n 2y agoNow this one makes more sense. Chemistry Nobel for advancing chemistry using AI. Contrast that with Phyics Nobel for advancing AI using physics.
- Muller20 2y agoAlphaFold is also a high impact discovery, while Hopfield networks have very little to do with modern AI and they are only a very interesting toy model right now.
- joelthelion 2y agoDid Demis Hasabis actually do any scientific work himself?
- deleted 2y ago[deleted]
- FL33TW00D 2y agoI mean he took the risk and founded DeepMind?
- belter 2y agoSo then Mustafa Suleyman and Shane Legg will want a Nobel also?
- onursurme 2y agoHe is a chemist now.
- seydor 2y agoYes in neuroscience. But i guess this one is recognition for leading efforts in RL which culminated in this.
- lennertjansen 2y agowell deserved
- aborsy 2y agoThe AlphaFold paper has countless authors, many researchers and company resources underlying it. Hassabis’ contribution is management of resources and entrepreneurship, not the actual science. There are hundreds of thousands of scientists out there doing deep technical work, and they aren’t recognized. I think we might be the end of it, as the emphasis shifts to commercialization and product development. These AI demonstrations require so many GPUs, specialized hardware and data that nobody has but the biggest players. Moreover, they are engineering work, not really scientistic (putting together a lot of hacks and tweaks). Meanwhile, the person who led the transformer paper (a key ingredient in LLMs) hasn’t been recognized. This will incentivize scientists to focus on management of other researchers who will manage other researchers who will produce the technical inventions. The same issue arises with citations and indices, and the general reward structure in academia. The signal these AI events convey to me: You better focus on practical stuff, and you better move on in the management ladder.
- world2vec 2y agoHasn't it always been like that? The lab director gets to receive the prize, not the whole team (which could have hundreds or thousands of people).
- bonoboTP 2y agoThe Nobel prize is aimed at the general public. It has a kind of late 19th century progressive humanistic ethos. It's science outreach. This way, at least once a year, the everyday layperson hears about scientific discoveries. The Nobel isn't a vehicle to recognize hundreds of thousands of deeply technical scientific researchers. How could it be? They have to pick a symbolic figurehead to represent a breakthrough. They could also simply give it to "DeepMind" similar to how they give the peace prize to orgs sometimes, or how the Time Person of the Year is sometimes something abstract as well (like the cutesy "You" of 2006). But it would be silly. Just deal with it, we can't "recognize" hundreds of thousands, and we want to see a personal face, not a logo of a company getting the award. That's how we are, better learn to deal with it.
- dsign 2y ago
- lr1970 2y agoHow come they missed Justin Gilmer? He did most of the original work [0]. [0] https://scholar.google.com/citations?view_op=view_citation&hl=en&user=Ml_vQ8MAAAAJ&citation_for_view=Ml_vQ8MAAAAJ:YsMSGLbcyi4C https://scholar.google.com/citations?view_op=view_citation&h... EDIT: typos
- DevX101 2y agoHere's a direct quote from the Alphafold paper: "These authors contributed equally: John Jumper, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Olaf Ronneberger, Kathryn Tunyasuvunakool, Russ Bates, Augustin Žídek, Anna Potapenko, Alex Bridgland, Clemens Meyer, Simon A. A. Kohl, Andrew J. Ballard, Andrew Cowie, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Demis Hassabis"
- seydor 2y agoThey didnt give the award to the paper
- onursurme 2y agoThe paper represents the work which lead to the prize. if A=B and A=C, then A=C
- SkiFire13 2y ago> if A=B and A=C, then A=C Technically true, but you might still want to double check your logic.
- fastball 2y agoNot all of the work. For example, it doesn't account for the fact that Demis Hassabis, as head of DeepMind, undoubtedly recruited many of the co-authors to participate in this effort, which is worth something when it comes to the final output.
- seydor 2y ago... and the Nobel in Economics goes to OpenAI for innovations in nonprofit business structures. it's the year of AI (ChatGPT preparing its acceptance speech)
- haunter 2y agoinb4 Nobel Peace Prize will go to Timnit Gebru
- belter 2y agoFirst Obama got the Peace Prize Nobel, now Demis Hassabis gets the Chemistry Nobel. I expect at a minimum the Nobel Prize in Literature to be Donald E. Knuth.
- deleted 2y ago[deleted]
- mihaaly 2y agoThe Nobel Prize in Literature should go to Jeff Bezos for the Amazon Kindle, obviously!
- belter 2y agoYeah, as the Head of the Engineering Org...Makes sense.
- boxed 2y agoI think a more fitting example would be to give the Literature Prize to my son, aged 8.
- Rochus 2y agoThe Nobel Committee is not unaffected by the global decline in IQ.
- deleted 2y ago[deleted]
- onursurme 2y agoCombine this with the Physics prize, I now have hope to receive a Nobel prize in any area. Seriously, from now on, I won't mention Nobel prizes anywhere anymore.
- LarsDu88 2y agoNobel committee is all in on the AI hype this year!
- balazstorok 2y agoNobel peace prize has countless times been awarded to a group of people or institution. It is differently controlled but the idea is not unprecedented.
- ascorbic 2y agoThe rules are different
- thatsadude 2y agoWell more deserving than the author of Restricted Boltzmann machine.
- ThePhysicist 2y agoDemis Hasabis has a really interesting and unusual CV for a nobel laureate [1], he started his career in AI game programming (he worked e.g. on Popoulous II, Syndicate, Theme Park for Bullfrog, and later for Lionhead Studios on Black & White) before doing a PhD in neuroscience, becoming an entrepreneur and starting DeepMind. I would say this is a refreshing and highly uncommon pick for a nobel prize, really cool to see that you don't have to be a university professor anymore to do this kind of impactful research. 1: https://en.wikipedia.org/wiki/Demis_Hassabis https://en.wikipedia.org/wiki/Demis_Hassabis
- seydor 2y agodoesn't beat that patent clerk guy
- singularity2001 2y agowhose father was one of the leading local industrialists (installing the first electric lighting for the 1885 Munich Oktoberfest)
- nextworddev 2y agoIt’s fascinating how the affluent backgrounds of many famous scientists and entrepreneurs are downplayed. Eg Warren Buffet, Jeff Bezos, etc
- xdavidliu 2y agoBill Gates, but (according to the Isaacson book) not Elon Musk
- concordDance 2y agoI'm now curious which of Gates, Musk and Bezos families were wealthier when they started their respective careers... I suspect Bezos, then Gates, then Musk, but it could be any order.
- mhrmsn 2y agoGreat achievement, although I think it's interesting that this Nobel prize was awarded so early, with "the greatest benefit on mankind" still outstanding. Are there already any clinically approved drugs based on AI out there I might have missed? In comparison, the one for lithium batteries was awarded in 2019, over 30 years after the original research, when probably more than half of the world's population already used them on a daily basis.
- pm215 2y agoArguably awarding early is more in line with the intention expressed in Nobel's will: "to those who, during the preceding year, have conferred the greatest benefit to humankind". It seems to have drifted into "who did something decades ago that we're now confident enough in the global significance of to award a prize". I suspect that if the work the prize recognized reslly had to have been carried out in the preceding year the recipients would be rather different.
- benrapscallion 2y agoShouldn’t this be GLP1RAs (semaglutide etc.) for the last year?
- cmavvv 2y agoGiven that drugs take around 10 years to get to market, and that some time is needed for industrial adoption as well, it's not very reasonable to expect clinically approved drugs before a few years.
- londons_explore 2y ago> around 10 years to get to market This is really sad. A new recipe for feeding honeybees to make tastier honey could get to market in perhaps a month or two. All the chemical reactions happening in the bees gut and all the chemicals in the resulting honey are unknown, yet within a matter of weeks its being eaten. Yet if we find a new way of combining chemicals to cure cancer, it takes a decade before most can benefit. I feel like we don't balance our risks vs rewards well.
- famouswaffles 2y agoYesterday's physics win was rather odd but this I have no problem with! Lol does this mean there's a chance the Transformer Authors win a Nobel in literature sometime? Certainly seems a lot more plausible than before yesterday.
- boxed 2y agoI think it's still too early to know if AlphaFold is a massively overfitted statistical model that will utterly fail on novel structures.
- patall 2y agoThe prize winners are ultimately selected by a group of mid-age to old professors. And to tell the truth (I work at a research institute in Stockholm), some of the old folks seem to have huge FOMO. They know that they cannot keep up themselves, they have no idea (and no way of finding out) who is actually good and who is just pretending, which leads to recruitment of an 'interesting' bunch of young group leaders. Some of them are surely good, but I know of at least one guy who holds presentations as if he invented AlphaFold himself, while having contributed one single paper of interest to the field. Large turn off for me.
- theGnuMe 2y agoI dunno, you should have AI FOMO. Or at least start focusing on computational thinking.
- patall 2y agoI do not criticize them for having FOMO. But I have my doubts when it is the 60-year-olds that are the most enthusiastic about something new (as long as it is not a new ABBA album), given the number of grifters out there. And there would have been many others that also deserve a Nobel, those three could easily have waited another 20 years. If it really was those that had the highest impact the last year who won the prize, it (or rather "Medicine") should have gone to GLP-1/Semaglutide research.
- theGnuMe 2y agoRight but this is a paradigm shift. If anything the 60 year-olds dumped on AI. Statisticians dumped on AI. Cybernetics/engineers all dumped on it. Just like everyone dumped on mRNA vaccines. I do agree with you about GLP-1 though that's legit as is the HIV vaccine. But still the way forward is computational thinking that is very clear.
- dist-epoch 2y agoCalling it, to keep with the theme: the Nobel prize in literature will be given to a LLM author.
- ConcernedCoder 2y agopeople still folding@home <shrug>
- cool-RR 2y agoI wonder why various outlets, including DeepMind's blog, say that John Jumper is a "Senior Research Scientist". That's L5 which sounds like quite a low rank for a Nobel prize winner. I checked his LinkedIn and he's a director, which is around L8. I thought that maybe he was L5 during the publishing of the results, but no, he was either L6 or L7.
- jltsiren 2y agoMaybe "Senior Research Scientist" sounds more respectable among the intended audience. A research scientist is usually an independent researcher rather than someone working in another person's team, while "senior" indicates that they have been in an independent role for a while. A director, on the other hand, is someone who failed to avoid administrative duties, and it doesn't imply any degree of seniority.
- tsimionescu 2y agoL5 doesn't mean anything to anyone outside of whatever organization you're talking about (Google?). A Senior Research Scientist means "a person who is a scientist, works in research, and is very experienced in that role". Even if this is not the title he holds in his organization, it is an objective title that applies to him.
- atmosx 2y ago> Oppenheimer was nominated for the Nobel Prize for Physics three times[...] pondered why he was never bestowed the honor. > “To understand this [...] you have to first examine the man’s academic life before and after the war.” Quote from: https://discover.lanl.gov/news/0609-oppie-nobel-prize/ https://discover.lanl.gov/news/0609-oppie-nobel-prize/ Not anymore. You're not required to know or have studied Chemistry to get a Nobel in Chemistry.
- famouswaffles 2y agoThe Nobel Prize has always prioritised advances in the field over specific training. Curie was a trained chemist when she won her prize in physics. Michelson was a Naval Officer. Of course naturally, being able to win a Nobel usually means you studied the field your entire life but that has never been a requirement.
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- ilaksh 2y agoFor some reason this web page doesn't render properly in my browser. The main text overlaps the table of contents. I'm using Chrome on KDE (Ubuntu) on a 1920 wide display (minus the side panel). I checked and I don't have the page zoomed. https://i.imgur.com/fOOQ3Av.png https://i.imgur.com/fOOQ3Av.png
- aithrowawaycomm 2y agoI think putting AlphaFold here was premature; it might not age well. AlphaFold is an impressive achievement but it simply has not "cracked the code for protein folding" - about 1/3rd of its predictions are too uncertain to be usable, it says nothing about dynamics, suffers from the same ML problems of failing on uncommon structures, and I was surprised to learn that many of its predictions are incorrect because it ignores topological constraints[1]. To be clear, these are constructive criticisms of AlphaFold in isolation, my grumpiness is directed at the Nobel committee. "Cracked the code for protein folding" is simply not true; it is an ML approach with high accuracy that suffers the same ML limitations of failing to generalize or failing to understand deeper principles like R^3 topology that cannot be gleaned stochastically. More significantly: it has yet to be especially impactful in biochemistry research, nor has its results really been carefully audited. Maybe it will turn out to deserve the prize. But the committee needed to wait. I am concerned that they got spun by Google's PR campaign - or, considering yesterday's prize, Big Tech PR in general. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672856/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10672856/
- InkCanon 2y agoI think looking back five years from now, this will be viewed as another Kissinger/Obama but wrt STEM. Given far too prematurely under pressure to keep up with the Joneses/chase the hype.
- aithrowawaycomm 2y agoI am not so confident or dismissive: the real problem is that testing millions of predictions (or any fairly bold scientific development like AlphaFols) takes time, and that time simply has not elapsed. Some of the criticisms I identified might be low-hanging fruit that in 5 years will be seen as minor corrections - but we're still discovering the things that need to be corrected. It is concerning that the prize announcement itself is either grossly overstated: With its help, they have been able to predict the structure of virtually all the 200 million proteins that researchers have identified [the word 'virtually' is stretched into meaninglessness] or vague, could have been done with other tools, and hardly Nobel-worthy: Among a myriad of scientific applications, researchers can now better understand antibiotic resistance and create images of enzymes that can decompose plastic. I am seriously wondering if they took Google / DeepMind press releases at face value.
- drpossum 2y agoNobel prize committee really sending some messages this year on what constitutes benefiting humanity the most.
- robertlagrant 2y agoThis was an incredible breakthrough.
- drpossum 2y agoDidn't say it wasn't.
- sega_sai 2y agoPhysics prize one goes to AI, chemistry too. What next? Nobel in Literature goes to ChatGPT? Jokes aside, I think the chemistry prize seems to make a bit more sense to me than physics one.
- theGnuMe 2y agoI think it is definitely possible for ChatGPT to win the Nobel Prize in Literature.. maybe not this version or the next but eventually -- especially if it is by proxy aka as is the premise in "The Wife" (a good book/movie btw). There's already precedent for anonymous creators, aka Banksy.
- bdjsiqoocwk 2y agoAnyone else think that giving a nobel prize to the CEO of the company is absurd?
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- eig 2y agoI think I disagree with most of the comments here stating it’s premature to give the Nobel to AlphaFold. I’m in biotech academia and it has changed things already. Yes the protein folding problem isn’t “solved” but no problem in biology ever is. Comparing to previous bio/chem Nobel winners like Crispr, touch receptors, quantum dots, click chemistry, I do think AlphaFold already has reached sufficient level of impact.
- singularity2001 2y ago>> I do think AlphaFold already has reached sufficient level of impact. how so?
- cmavvv 2y agohttps://www.pnas.org/doi/10.1073/pnas.2315002121 https://www.pnas.org/doi/10.1073/pnas.2315002121
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- eig 2y agoWell I'm sure one could look at number of published papers etc, but that metric is a lot to do with hype and I see it as a lagging indicator. A better one is seeing my grad-school friends with zero background in comp-sci or math, presenting their cell-biology results with AlphaFold in conferences and at lab meetings. They are not protein folding people either- just molecular biologists trying to present more evidence of docking partners, functional groups in their pathway of interest. It reminds me of when Crispr came out. There were ways to edit DNA before Crispr, but its was tough to do right and required specialized knowledge. After Crispr came out, even non-specialists like me in tangential fields could get started.
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- mensetmanusman 2y agoYou know they actually made a huge chemistry breakthrough though?
- YeGoblynQueenne 2y agoLooks like science is out, black box prediction is in. It's like the era of epicycles all over again. Oh well. Fellow realists, see you all 1500 years from now!
- pelorat 2y agoThere are things so complex in science that a human mind can never understand them, but a large neural network can.
- outworlder 2y agoFor some definition of 'understanding'.
- YeGoblynQueenne 2y agoConjecture, that. Even if true I think it will be very hard to find any definition of science along the lines of "training deep neural nets to do the understanding in our stead".
- bonoboTP 2y agoIt was big blind luck that the laws of planetary motion turned out to be so simple. There's no reason to think that protein folding can similarly be reduced to some elegant description without needing large blackbox models.
- ayakang31415 2y agoScience is just a methodology to test hypothesis. It does not matter how you get the result as long as the result is empirically scrutinized.
- tim333 2y agoDunno. It's a tool to try to figure the shape of molecules in a similar way that a cryo-electron microscope is a tool for that. Not the end of science imho.
- uptownfunk 2y agoTo me this is more controversial than Geoffrey Hinton winning it for physics.
- ocular-rockular 2y agoThey should've given this prize to Hinton too, for making the machine learning of Alphafold possible.
- dekhn 2y agoI wasn't expecting to see David Baker in the list (just Demis and John). But I'm really glad to see it... David is a great guy. At CASP (the biannual protein structure prediction competition) around 2000, I sat down with David and told him that eventually machine learning would supplant humans at structure prediction (at the time Rosetta was already the leading structure prediction/design tool, but was filled with a bunch of ad-hoc hand-coded features and optimizers). he chuckled and said he doubted it, every time he updated the Rosetta model with newer PDB structures, the predictions got worse. I will say that the Nobel committee needs to stop saying "protein folding" when they mean "protein structure prediction".
- jboggan 2y agoThe models and tools designed for the CASP competition were an example of running around the solution space at a glacial pace and getting stuck in local minima. I can't speak for Rosetta by my labmates had fairly successful tools that usually ranked right behind Baker's lab, and they were plagued by issues where the most successful models had impossible or idiosyncratic terms in them. For example, a very successful folding model had the signs reversed on hydrophobic and some electrostatic interactions. It made no sense physically but it gave a better prediction than competing models, and it was hard to move away from because it ranked well in CASP.
- dekhn 2y agoWhich model had the signs reversed? Yes, CASP was prone to getting stuck in local minima. I think the whole structure prediction field had become moribund.
- throwawaymaths 2y agoRefreshingly good. Bakers "early" (not really early, but earlier than AlphaFold) work (having humans with no background solve folds) really laid the groundwork to proving that heuristic methods were likely to outperform physical forcefield and ab initio/DFT methods for structure prediction. And AI structure prediction if nothing else is heuristic protein folding.
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- hanjeanwat 2y agoexcellent longread on the development of AlphaFold - with interviews with Baker + Jumper and more: https://www.quantamagazine.org/how-ai-revolutionized-protein-science-but-didnt-end-it-20240626/ https://www.quantamagazine.org/how-ai-revolutionized-protein...
- jboggan 2y agoCongrats to David Baker and his lab!
- photochemsyn 2y agoAlphaFold is a useful tool but it's unsatisfying from a physical chemistry perspective. It doesn't give much if any insight in to the mechanisms of folding, and is of very limited value in designing novel proteins with industrial applications, and in protein prediction for membrane-spanning proteins, extremophilic microbe proteins, etc. Thus things like folding kinetics of transition states and intermediates, remain poorly understood through such statistical models, because they do not explicitly incorporate physical laws governing the protein system, such as electrostatic interactions, solvation effects, or entropy-driven conformational changes. In particular, environmental effects are neglected - there's no modeling of the native solvated environment, where water molecules, ions, and temperature directly affect the protein’s conformational stability. This is critical when it comes to designing a novel protein with catalytic activity that's stable under conditions like high salt, high temperature etc. As far as Nobel Prizes, it was already understood in the field two decades ago that no single person or small group was going to have an Einstein moment and 'solve protein folding', it's just too complicated. This award is questionable and the marketing effort involved by the relevant actors has been rather misleading - for one of the worst examples of this see: https://www.scientificamerican.com/article/one-of-the-biggest-problems-in-biology-has-finally-been-solved/ https://www.scientificamerican.com/article/one-of-the-bigges... For a more judicious explanation of why the claim that protein folding has been solved isn't really true: "The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins" (June 2024) https://www.nature.com/articles/s41589-024-01638-w https://www.nature.com/articles/s41589-024-01638-w
- pelorat 2y agoThe mechanisms of folding is most likely impossible for a human mind to comprehend.
- LarsDu88 2y ago[flagged]
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- bawolff 2y agoAI is cleaning up at the nobel prizes!
- optimalsolver 2y agoThis is what extreme FOMO looks like.
- muenalan 2y agoSurely, it is helpful to consider the achievement in terms of the contest setup to detect a Nobel-worthy breakthrough: https://en.m.wikipedia.org/wiki/CASP https://en.m.wikipedia.org/wiki/CASP It moved the needle so much in terms of baseline capability. Let alone Nobel’s original request: positive impact to humanity; well deserved. In biology/medicine it is still awed like coming from a different planet; tech before was obviously that lacking.
- hilux 2y agoI'm not always a Lex Fridman fan, but the interview with Demis is well worth a listen.
- blackeyeblitzar 2y agoFirst physics and now chemistry. I wonder if we’ll see AI/ML-powered work in most prizes going forward.
- phtrivier 2y agoFeeling a bit down today, so just asking: when can we realistically expect to see the (positive) effects of this Nobel in daily life, and what would they be ? (I understand it's helping biotech a lot, but helping them do... what exactly ?)
- Dumblydorr 2y agoThe drug development process takes around 10+ years typically, a lot of long planning of multiple phases of studies needs to be done. This will help in the initial steps and in finding good starting points, and in theory should help the subsequent stages be more successful. I wouldn’t expect new drugs this decade. Other aspects of biotech and research could well be affected far faster than the consumer drug market, but again you’ll need a few years for those early stage developments to aid real world applications.
- kragen 2y agoHuh, so both the chemistry Nobel and the physics Nobel were for neural networks this year. That's astounding.
- muziq 2y agoNice one Demis & Chums!
- ggm 2y agoAs a computer scientist who is oppositional to AGI boom-bubble mania, it was easy to decry the Nobel in physics. But, contextually given who Murray Gell-Mann was and what field he was in (astrophysics) I feel a very strong Gell-Mann Effect here because I am happy to accept THIS use of computational systems to advance (bio)chemistry is worthy, and I find myself wondering why I am so uncritical about it?
- puzzledobserver 2y agoI see a number of comments here about giving awards to organizations rather than individuals, and counter-comments pointing out that Nobel's will disallowed it. How is the Nobel Prize actually administered? For how long is the Nobel committee bound to follow Alfred Nobel's will? And aren't there laws against perpetual trusts? Or is the rule against awarding the technical awards to organizations one that the committee maintains out of deference to Nobel's original intentions?
- lysozyme 2y agoFor those like myself who design proteins for a living, the open secret is that well before AlphaFold, it was pretty much possible to get a good-enough structure of any particular protein you really cared about (from say 2005) by other means, namely Baker’s Rosetta. I constantly use AlphaFold structures today [1]. And AlphaFold is fantastic. But it only replaces one small step in solving any real-world problem involving proteins such as designing a safe, therapeutic protein binder to interrupt cancer-associated protein-protein interactions or designing an enzyme to degrade PFAS. I think the primary achievement is that it gets protein structures in front of a lot more smart eyes, and for a lot more proteins. For “everyone else” who never needed to master computational protein structure prediction workflows before, they now have easy access to the rich, function-determinative structural information they need to understand and solve their problem. The real tough problem in protein design is how to use these structure predictions to understand and ultimately create proteins we care about. 1. https://alexcarlin.bearblog.dev/multistate-protein-design-with-alphafold-and-proteinmpnn/ https://alexcarlin.bearblog.dev/multistate-protein-design-wi...
- throwawaymaths 2y agoForget Rosetta. Even installing that shit was hard, and running it on a sufficiently beefy machine was probably really not a thing in the late aughts. For protein design you mostly just need a quick and dirty estimate of what it looks like, and you have friend proteins that can be used to homology map, you could just use phyre/phyre2, which is an online threading model and be close enough to get work done. Upload the pdb, upload the sequence, bing bam boom.
- hackernewds 2y agoRosetta was clunky and not even David Baker would endorse it
- moralestapia 2y agoCitation needed. I worked on protein structure prediction for a couple years and it was sota.
- zmmmmm 2y agoSo between this and the award for physics, it's basically a clean sweep of the Nobel prizes this year for AI. Quite a moment if you stand back and think about that.
- drumhead 2y agoIts the AI Nobels. First physics and now chemistry. Demis Hasabis getting the prize for Chemistry is not something I would have ever expected though.
- pagade 2y agoPrediction: Demis Hasabis will win second Nobel.