8 ms·
AlphaProteo generates novel proteins for biology and health research
- bluehat974 2y agoTwo minute papers video on the subject: https://www.youtube.com/watch?v=lI3EoCjWC2E https://www.youtube.com/watch?v=lI3EoCjWC2E
- deisteve 2y agoi studied molecular biology and i couldn't help contain my excitement when it was able to bind to another protein. I dont think HN realizes how huge this is. With this level of accuracy, not only can we understand the full mysteries of ourselves but literally any biological entity. With that level of understanding, its easy to fabricate special medicines that target specific biochem pathways, but more exciting is that we can literally "code in 3d world". We'll be able to print and grow organs in mass. We'll be able to design structures that will bind to target proteins responsible for certain traits. The potential boon to human medicine will be enormous. I got like goosebumps after watching that video because I understood the implications of being able to predict folds and now generate proteins that will bind to any protein we choose!!!! We just might have discovered a panacea of sorts and Demis and his team should receive the Nobel Prize. I'm just ecstatic that we'll see so much drastic improvement in human medicine and importantly how accessible they will be with this new discovery.
- holoduke 2y agoIn 2035 everybody can live forever.
- kridsdale3 2y agoHow do you feel about the potential bioterrorism alternate angle of this capability?
- deisteve 2y agoit would be like committing terrorism using silicon wafers you would have to infiltrate an extremely guarded facility you would somehow have to bypass QA its not like somebody on the assembly line for a new protein drug sprinkles a dose of PCP one potential dual use could be somebody modifying a popular fruit with birds and then droppin seeds at the local organic farm fair and then when those seeds are consumed by birds they produce poop dangerous for other animals to consume you could absolutely screw around with the ecosystem, like whoever has access to this programmable "bio-wafer" will be able to play god totally undetected. the problem is that "bio-wafer" manufacturing process will be very tough and regulated like the CNC machines used to manufacture jet engines depriving certain countries from being able to churn out their own jet engines
- mjcohen 2y agoIts not regulated if a government does it.
- kemmishtree 2y agoIf you haven't heard the phrase "utility-scale molecular sensing" or given it any thought, please prepare to update every opinion you might have about bioterrorism, and ask Keltar how the MR1 is our greatest plausible non-authoritarian line of defense. www.molecularreality.com Keltar is the little green guy in the upper left.
- kemmishtree 2y agoOh and don't get an account it's broken right now, I'm building the site and hardly anyone has been there yet and the Auth0 is fucked up. But just give your email to Keltar if you wanna followup.
- deisteve 2y agoLMAO this is some low effort LLM
- 2y ago
- stanford_labrat 2y ago> We'll be able to print and grow organs in mass. I'm a PhD candidate doing my thesis work on stem cell models and tissue engineering for organ transplant...I think this technology is certainly a large leap forward but I think you are a little overzealous with this claim.
- aquafox 2y ago> With that level of understanding, its easy to fabricate special medicines that target specific biochem pathways The problem is to find the right target or pathway in the first place. Just go to opentargets.org. There are lots of potential targets by different metrics but for many diseases we haven't identified that single target that let's us improve the life of say, 20% of patients, for disease X.
- nextos 2y agoEngineering biology is much much harder than simply knowing approximately how to fold proteins. Obviously folding proteins is an important first step. Arc Institute and others are already looking at whole cell models, i.e. systems biology. It's a totally different level of abstraction.
- m3kw9 2y agoLet’s see a real drug coming out of this then we can talk
- ramraj07 2y agoThat channel is just hype machine. Like half the stuff he says is barely comprehensible if you know the actual science.
- kick_in_the_dor 2y agoWhen he started the video with "I had the honor of having an exclusive look at it" I knew it was all marketing.
- throwaway314155 2y ago[flagged]
- westurner 2y ago> Trained on vast amounts of protein data from the Protein Data Bank (PDB) and more than 100 million predicted structures from AlphaFold, AlphaProteo has learned the myriad ways molecules bind to each other. Given the structure of a target molecule and a set of preferred binding locations on that molecule, AlphaProteo generates a candidate protein that binds to the target at those locations.
- sdenton4 2y ago(not to be confused with AlphaProto, which is helps with Google's core business of turning protocol buffers into differenter protocol buffers.)
- purpleblue 2y agoI wonder how many prions will be accidentally created by this, or if it can even predict if a particular protein will have prion-like effects
- DalasNoin 2y agoThe context here is that prions are misfolded proteins that replicate by causing other proteins to change their configuration into the misfolded form of the prion. Diseases caused by prions include Mad Cow disease, Creutzfeldt-Jakob disease, and Chronic Wasting disease. All prion diseases are incurable and 100% fatal.
- nabla9 2y agoIf the protein is a novel it does not matter, because it has no normal variants in the nature.
- connorgutman 2y agoCouldn’t the underlying tech be applied to non-novel proteins by a bad actor?
- DalasNoin 2y agoSomeone could fine-tune a model on pairs of existing proteins and their misfolded prions and then ask the system to come up with new prions for other proteins. ChatGPT found these 4 companies that will produce proteins for you just based on digital DNA that you send them: - Genewiz (Azenta Life Sciences) - Thermo Fisher Scientific (GeneArt) - Tierra Biosciences - NovoPro Labs
- connorgutman 2y agoWhelp, time to move to a small island in the middle of the Pacific.
- ben_w 2y ago
- eig 2y agoMaybe this is in the supplement of the whitepaper [0], but I would have loved to see more analysis of how novel the designed proteins really are. In the whitepaper they mention that they are novel compared to other in silico design techniques, but to my knowledge other binders to VEGF and Covid spike protein exist and would already be found in the PDB database that Deepmind trained the model on. This is not to minimize the results- if the history of ML is anything to go by, even if AlphaProteo does not currently beat the best affinity found by in vitro screens, I do not doubt that it soon will! [0] - https://storage.googleapis.com/deepmind-media/DeepMind.com/Blog/alphaproteo-generates-novel-proteins-for-biology-and-health-research/AlphaProteo2024.pdf https://storage.googleapis.com/deepmind-media/DeepMind.com/B...
- vessenes 2y agoThey must be somewhat novel in that the wet lab work verified up to 10x stronger binding as predicted. I agree it would be interesting to see how they compare to known binding proteins
- dekhn 2y agowe've been able to design tight binders for quite some time now- the issue with synthetic designs is that they tend to bind a little too tightly. You want to have a reasonable off-rate and the ligand protein should do more than just bind, it needs to effect some sort of response from the bound protein. When you look at these synthetics they often maximize for interactions of hydrophobic areas on the surface.
- gilleain 2y agoMight depend on what your measure of 'novelty' is in protein structure. A single residue change (for example) would not normally be considered a novel structure - it's just a mutation. However, a new fold - that is, the shape that the backbone folds into - would be novel. Potentially also novel would be 'chimeric' structures with parts from other structures, as with chimeric domain swaps. There was a structure designed by the Baker lab called 'Top7 - https://pubmed.ncbi.nlm.nih.gov/14631033/ https://pubmed.ncbi.nlm.nih.gov/14631033/ that I remember as ground breaking at the time :) (in the ancient days of 2003 it seems ...)
- i_love_limes 2y agoI have a question that hopefully a molecular biologist can answer. Can tools like this potentially create protein structures that specifically bind in certain cells? Or is this more about a way of being able to create proteins for genes / structures we haven't been able to before? I'm very interested in my research at the moment in pleiotropy, namely mapping pleiotropic effects in as many *omics/QTL measurements and complex traits as possible. This is really helpful for determining which genes / proteins to focus on for drug development. The problem with drugs is in fact pleiotropy! A single protein can do quite a lot of things in your body, either through a causal downstream mechanism (vertical pleiotropy), or seemingly independent processes (horizontal). This limits a lot of possible drug target as the side-effect / detrimental effect may be too large. So, if these tools can create ultra specific protein structures that somehow only bind in the areas of interest, then that would be a truly massive breakthrough.
- _yb2s 2y agoYes, in principle but there are huge limitations and challenges to using a protein as a drug in living organisms. It has to be injected to avoid digestion, and a protein can't just pass into a cell, it needs to get in somehow. Current peptide drugs like insulin are identical to, or closely mimic natural small peptide hormones that bind to receptors on the outside of a cell. However, there is a possibility of using gene therapy to directly express a novel protein drug inside of the cell. A novel protein is also likely to trigger an immune response- so that type of gene therapy is mostly useful when that is actually desired, e.g. as a vaccine.
- Pulcinella 2y agoFor anyone who would like to know more about designing proteins with a certain function, target, or structure in mind, the term to search for is "rational design." https://en.m.wikipedia.org/wiki/Rational_design https://en.m.wikipedia.org/wiki/Rational_design
- ampdepolymerase 2y agoAlso "off target effects".
- gman83 2y agoWhat is Google actually doing with these systems? Are they using it to develop new drugs themselves? Or licensing it to the pharmaceutical industry?
- skadamat 2y agoCynical take - mostly to appear like a diverse tech company with lots of different products and services so they don't get regulated for their strength in the search advertising market.
- aurareturn 2y agoI think occam's razor might suggest they're trying to diversify their revenue so if search declines, they have fallbacks.
- faceloss 2y ago[dead]
- DiscourseFan 2y agocould be both
- kridsdale3 2y agoAs a Google engineer, I think it's two things: - Great for recruitment: You're the most talented $SKILL in the world? Come to the team that is pushing humanity forward in all the ways that matter. - Larry and Sergei actually care about humanity, and being a billionaire is kind of a side-effect of what they would have done anyway.
- bawolff 2y agoIts not like google is the first company to have a will R&D department. Xerox invented the mouse. AT&T invented unix & c. Etc
- 2y ago
- idunnoman1222 2y agoIt generates novel candidates doesn’t actually generate proteins, and none of these proteins have actually been generated to validate whether these candidates are shit or not
- pertymcpert 2y agoDid you read it?
- idunnoman1222 2y agoThis is equivalent of ChatGPT generates novel code, but we didn’t run it. It probably works though.
- vessenes 2y agoTerrible take. The article details independent lab verification with researchers listed by name and a quote from them.
- pertymcpert 2y agoMaking a comment without reading the article? Who would do such a thing?
- photochemsyn 2y agoInteresting work, but there's a huge sector they're missing - industrial enzyme and catalysis design. Most of this field is concerned with small molecule binding - methane, carbon dioxide, ammonia, methanol, acetic acid, etc. Binding is often just the first step, as you're typically trying to do highly specific chemistry, e.g. attaching a single oxygen to methane or a single hydrogen to carbon dioxide, etc. Working in this area might also be good test of their technological approach, as small-molecule binding can be somewhat challenging, and even evolved biological systems can struggle to achieve high specificity.
- dekhn 2y agoI want to mention an interesting industrial enzyme project. If you ever saw the laundry detergent commercial "Protein gets out protein", this is referring to an industrial enzyme in laundry detergent. Many years ago, Genentech had built up a significant capability in proteases, which are proteins that cut other proteins into pieces. In the course of optimizing proteases, they made a thermostable, thermoactive protease. Although it wasn't super useful for Genentech in a drug discovery context, it was recognized that you could put an inactive enzyme into laundry detergent that would be activated when the hot laundry water hit the detergent, and the resulting protease would be good at cleaning stains (many stains are composed of protein- blood, food, etc). Genentech set up a subsidiary with Corning (the glass company) that owns the IP for this protease and then licensed it to laundry detergent manufacturers; many billions of dollars in revenue. I think this is one of the original patents: https://patentimages.storage.googleapis.com/d9/ca/6f/2fb89fff81ae44/US4760025.pdf https://patentimages.storage.googleapis.com/d9/ca/6f/2fb89ff...
- ray__ 2y agoMy guess is that this area is much harder to break into–enzymes facilitate challenging chemical transformations by stabilizing high-energy transition states in chemical reactions. These states are usually highly transient and therefore much harder to capture using the structural biology techniques that generate the structural data that AlphaFold and similar methods are trained on. Even though there are many structures of enzymes in the absence of their substrate, I would imagine that the small number of structures for states that represent actual catalytic intermediates would make it difficult for a model to internalize the features that distinguish a good enzyme/catalyst from a bad one. Another consideration is that most protein structure prediction methods only generate the backbone, and the sidechains are modeled in afterwards. Enzyme efficiency requires sub-A level structural precision in the sidechains that are actually doing the chemistry involved in catalysis, so it could also be the case that the current backbone-centric methods aren't good enough to predict these fine-tuned interactions.
- pokot0 2y agoSafety is the new gatekeeping.
- cultofmetatron 2y agonew?
- VyseofArcadia 2y agoIt's extremely refreshing that DeepMind is still working on using AI to solve hard problems instead of attempt to put creatives out of work.
- gman83 2y agoI wonder if the backlash they received from inventing transformers and then allowing OpenAI to eat their lunch has changed their attitude towards how they'll commercialize future inventions.
- _p2zi 2y agoI am sorry for my naivety, but what is the practical benefits of this?
- space_fountain 2y agoIt varies, but as the article says it can be used for things like drug discovery. Imagine there's a new virus running rampant. It works by using a very specific protein to latch onto a cells so it can pull itself in. You would like to develop a drug to stop it doing that and one way to do that is to find a protein that wants to strongly latch on to an important part of the virus. If it's holding onto the virus the virus probably won't be able to penetrate cells because you're engineered protein will get in the way. This is part of how antibodies work to stop viral infections naturally
- letitgo12345 2y agoOne question is how specific the binding is -- what's the level of off-target effects, etc.
- flobosg 2y agoIn my humble opinion, this work is not that innovative: de novo protein binders have been done to death, either by AI approaches or otherwise. Check out the work by David Baker’s group, for instance. They have a myriad of examples already. That being said, as others have commented, my hopes are that all these advancements lead finally to reliable design methods for novel biocatalysts, an area that has been stalling for decades, compared to protein folds and binders.
- lysozyme 2y agoAgreed on the hopes that these methods lead to novel biocatalysts (but they aren’t quite there yet). David Baker’s lab has recently published on using their own diffusion model (RFdiffusion) to design novel biocatalysts that perform hydrolysis using a catalytic triad of serine, aspartic acid, and histidine, as well as an oxyanion hole, which is much more complex than the binders designed by AlphaProteo [1]. It gives me hope that we’ll soon be able to design biocatalysts as good as natural ones, but for any problem we care about. 1. https://alexcarlin.bearblog.dev/novel-enzymes-from-a-diffusion-model-paper-review/ https://alexcarlin.bearblog.dev/novel-enzymes-from-a-diffusi...
- flobosg 2y agoYeah, I checked the preprint. Engineering serine hydrolases is kind of a low-hanging fruit, but a great starting point nevertheless!
- maxc99 2y agoYeah, I agree. Honestly I found AlphaFold 3 to be way overblown as well. Engineering new biocatalysts is exactly what my group is working on rn.
- boywitharupee 2y agowhat kind of model architecture was used for this? is it safe to assume they used a transformer model or a variant of it?
- animanoir 2y agoyeah yeah whatever another protein discovered oh wow... When are we going to see actual results? Hurry up Deepmind!
- muaytimbo 2y agoThis is interesting work but I think something has been intentionally overlooked. Creating proteins is difficult and it's also unclear how many of these sequences folded into the predicted 3d structure. Small molecule synthesis is still easier, cheaper, and more scalable than protein therapeutics. I think this would've been more impactful had they focused on improving on the SOTA small molecule - protein interaction models.
- flobosg 2y ago> it's also unclear how many of these sequences folded into the predicted 3d structure The whitepaper depicts some successful cases, determined by X-ray crystallography or cryo-EM.
- parhamn 2y agoQuestion for bio folks here, and not to steal from the joy of this article but I've been recently curious how far are we from engineering something like a virus that targets a subset of the population (e.g. via specific genetic markers). This sort of tech being commoditized feels much much scary than the LLM safety talk - by a mile.
- bongodongobob 2y agoMaking proteins is nothing like designing life or viruses. It's barely even related.
- parhamn 2y agoYeah I figured as much. Hence the "[t]his sort of tech" -- I imagine progress would be made soon on those fronts as well? Or am I mistaken?
- bongodongobob 2y agoThis sort of tech is like inventing a new type of screwdriver and asking how it will affect car production.
- parhamn 2y agoNot helpful.
- puzzlingcaptcha 2y agoI'm going to play the devil's advocate and disagree. The viral life-cycle comprises attachment/entry, replication and maturation/release. These stages are generally well understood to the point where 'disarmed' (replication-incompetent) viruses are routinely used as a delivery vehicle in molecular biology. The first part, attachment/entry is directly related to protein-protein interactions (between the envelope protein of the virus and the entry receptor of the host cell). This particular interaction determines the tropism of the virus, that is, its capability to infect a particular type of cell. Examples include the interaction of gp120 protein of the HIV virus and CD4 of a helper T cell, or the spike protein of SARS-CoV-2 and ACE2 of nasal ciliated cells. The parent specifically asked about targeting a group of people - designing an envelope protein (or proteins) targeting a specific HLA haplotype would probably get you halfway there (this is not advice).
- kemmishtree 2y agoI only comment on hacker news posts about biology because I'm a voice crying in the wilderness about the most important goddamn startup on Earth, I think, maybe. www.molecularReality.com
- fsndz 2y agoany resources to self learn biotech and how to use ML in biotech ?
- swframe2 2y agoI saw a recent video about the errors of alphafold 3. https://www.youtube.com/watch?v=E61wJXlENoE https://www.youtube.com/watch?v=E61wJXlENoE
- mike_hearn 2y agoThat video is saying that AlphaFold isn't good at predicting how proteins bind to each other, but is actually pretty good at predicting the structure of the individual proteins. Which is exactly what you would expect, because AlphaFold wasn't designed to predict antibody/antigen bindings. That's what AlphaProteo is now trying to solve. Also, as the video points out at the end, AlphaFold is well aware that it's unable to do this task and is communicating that fact via its ultra low confidences in the accuracy of the positioning of the proteins relative to each other. So I am not really sure what this video is trying to prove.
- motyar 2y agoThis could go wrong, in many directions