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Coronavirus Spike Protein Binder Design
- Aissen 7y agoI know it's fun, and I think participative science is such a huge shift in paradigm … But considering the global impact of coronavirus, I'm wondering if there shouldn't be a better way to fund this type of endeavor. Any cloud provider willing to donate compute to researchers?
- sschueller 7y agoHow about the government giving access to its huge computing power or commandeering free resources at large providers for the common good?
- gruez 7y ago>commandeering free resources at large providers for the common good? Sounds like a good way to get every cloud provider to pull out of your country.
- _Wintermute 7y agoThe research institutes I've worked at have all had copious amounts of compute resources usually freely available to reserarchers. I'm not in this field, but I really don't think compute power is the limiting factor in stopping this outbreak.
- usrusr 7y agoYeah, if you could somehow just trade compute for cure... Got a minor chuckle out of the hypothetical that the virus could somehow be defeated with hashrate: poor thing wouldn't know what hit it.
- cowsandmilk 7y agofold.it is a lot more about the fact that humans still are a lot better at exploring complex spaces than computers. Analysis of results has shown players reaching semi-global minima in folding space much quicker than computers and designing novel folds that express and crystallize that have not been seen in nature before (which means they can explore more space than starting from known templates). Researchers are trying to learn from the types of moves that humans make in the game to improve algorithms, but humans are still better at searching, making very productive large moves in folding space. So basically, this is less about funding and more about the fact that our algorithms aren’t good enough.
- Aissen 7y agoThanks for the context, I remember now, I had completely missed this part. Your comment should be at the top of the thread.
- moomin 7y agoSo close, and yet so far... What you're looking for is a well-funded public health system. And to vote out politicians that defund healthcare.
- ppf 7y agoPublic health systems, well-funded or not, are not a cure-all. I'd be curious to hear if you have any examples - if anything, they are reliant on research funded by the huge amount of money sloshing around the US healthcare system. Given a fixed annual budget, a public health system essentially has to decide what "healthy" or "cured" means, and set some quality of life to cost of treatment ratio. Some examples: my dad, an incredibly fit ultra-runner, suddenly found himself unable to run more than a few miles, and was gasping for air. He was initially told he was fine for his age, and had to fight for further diagnosis. A close friend of my wife's died of bowel cancer - this is a known "loophole" in the diagnosis pathways of our public health care system. Essentially, it was decided that the cost of early diagnosis is too high for the relatively tiny amount of people who have it, which is why most cases are found when they are terminal.
- nolongerlowres 7y agoI’m sorry to hear about your wife’s friend. But both examples you gave (people having to fight for further diagnoses of outside-case health problems) are really common with private healthcare in the United States too - we’ve just shifted the burden of cost of treatment/quality of life decisions to private entities who typically are only interested in furthering shareholder value. To give a personal anecdote as well: A close friend of my wife’s had to fight and fight to get insurance to cover appointments in order to get her breast cancer diagnosed. I would like to understand if the world really does rely on US private-healthcare funded research - I’ve heard this argument mentioned before and have always been curious about it.
- ppf 7y agoAgreed, the US system is flawed. I suppose with public-funded healthcare, everyone is on the same level - the survival rates of breast cancer and bowel cancer is the same for all (unless you can afford to fly to the US and pay for care there).
- dekhn 7y agoThe big cloud providers already donate a fair amount of compute (for example, some time ago I ran exacycle, which provided teams like FOlding@Home and Rosetta with extensive computing power. However, the economics of cloud are such that nearly all large-scale compute needs to provide revenue to the cloud provider for the provider to stay competitive. I've worked with the US gov't funding agencies in the past to make it possible to get "cloud credits" instead of grant $$$ (and even sat on panels that selected grants to promote cloud computing over closet clusters). The US works quite slow. IIRC, fold.it is from David Baker, and he has a stable funding pipeline due to the sucess of Rosetta.
- chapium 7y agoGovernments have a staggering amount of computational power. Good will is nice and all, but are we putting our tax payer funds to an obvious public need?
- dekhn 7y agoDo they? I mean, technically the US gov't leases a ton of desktops (not great for scientific/technical computing), and they own a few supercomputers for specific needs (national defense, weather), but mostly they fund modest computational centers in academic environments. Before cloud, I worked in grid, and grids strapped together the many academic and government clusters, mainly for embarassingly parallel workloads. I don't think the government has shown itself to be a particularly skilled operator of large computing environments compared to the large cloud providers.
- zedr 7y agoFascinating... What are the odds against finding this particular type of antagonist protein?
- rolph 7y agoits already found, its just the finer details have to be investigated before it becomes a legit treatment.
- amelius 7y agoIf you find a protein that blocks the virus, how difficult would it be to find a drug delivery mechanism that is capable of reaching all the important cells?
- pas 7y agoIsn't blood pretty good at this?
- hkt 7y agoOnly if you want to deliver indiscriminantly
- Gravityloss 7y agoA lozenge? A nose spray?
- rolph 7y agoyes that is workable but a nebulizer is what is currently being proposed.
- amelius 7y agoI'm not a biologist but I suppose that not every kind of protein enters any kind of cell.
- sp332 7y agoYou need these proteins to interfere with viruses before they enter cells, so that part is probably fine.
- pas 7y agoWhere the virus can go the antiviral can go too (because it's much smaller, only targeting a smaller protein spike on the surface of the viral envelope). https://en.wikipedia.org/wiki/Coronavirus#/media/File:3D_medical_animation_corona_virus.jpg https://en.wikipedia.org/wiki/Coronavirus#/media/File:3D_med... [the N protein is supposedly the nucleocapsid, which is basically/maybe another envelope around the RNA]
- hkt 7y agoHN hug of death?
- russfink 7y agoDown at 6:52 ET
- rckoepke 7y agoIntermittent. Reloading sometimes makes it work. Probably best not to reload multiple times, that multiplies the hug of death effect. Just bookmark it and come back later. I feel silly, I've known about fold.it and fold@home for years now, but somehow interpreted this title as a design for a binder, like a printable cosmetic insert for a school binder.
- tyingq 7y agoDrupal without caching is a dog. Often hundreds of database queries for a single page. 63 requests to render that page too. Looks like it might be back up now though.
- cbg0 7y agoMirror: http://archive.is/y67Ig http://archive.is/y67Ig
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- hditorkeif 7y agoThis is what antibodies do, right? How exactly does the body figure out how to configure the variable part of the antibody so that it binds? Does it just try countless variations until it finds a match? Can we take an antibody from a healed person and reverse engineer the binding protein?
- candiodari 7y agoYes and no. Antibodies bind against essentially anything on the virus surface, and (depending on the exact type of antibody) do that to multiple virus particles. This is often enough to prevent the membrane from successfully merging with a cell and therefore prevents or seriously reduces the infection rate (you don't have to get infection rate to zero, just low enough). Additionally these antibodies are collected and expelled by other parts of the immune system. But afaik the immune system does nothing to target active sites. This makes sense: specificity matters. For example disabling HIV is easy: just prevent CD4 binding. That will prevent the virus from attacking any human cell. Unfortunately, it has the same effect as AIDS, over time it cripples the immune system. You want to bind, not to the active sites, but to whatever is on the virus and isn't on anything else.
- gmm1990 7y agoYeah probably an oversimplification but it just creates different combinations and the ones that attach to the pathogen (and don't attach to non-pathogenic things in the body) are reproduced. But the immune system is wild I would say comes close to the neurological system from a how does this exist perspective. https://en.wikipedia.org/wiki/Antibody#Immunoglobulin_diversity https://en.wikipedia.org/wiki/Antibody#Immunoglobulin_divers...
- littlestymaar 7y ago> How exactly does the body figure out how to configure the variable part of the antibody so that it binds? Does it just try countless variations until it finds a match? Not a biologist but IIRC, the body produces cells with a shuffled sequence of DNA. Then this specific cell produces one specific variant of antibodies, located on its surface. At this point the antibody is just a random sequence that matches with nothing. If one day a virus (or anything else) happen to match with the antibody located on the surface of the cell, the cell will then multiply and most of the new cells will specialize into antibody-producing cells (released in the body, not remaining on the surface of the cell) and a small amount will not. The one who aren't producing antibodies are kept in the body for a long time, and they are here to provide quick specific response next time you meet the pathogen again (that's where immunity comes from). So yeah, it's basically brute-force until a matching antibody is found.
- DrAwdeOccarim 7y agoThere is already stuff like this out there: https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2.full.pdf https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2.... Also, it appears as though convalescence therapy is working (i.e., treating people with the plasma from recovered patients) https://www.straitstimes.com/asia/east-asia/china-seeks-plasma-from-recovered-patients-as-coronavirus-treatment https://www.straitstimes.com/asia/east-asia/china-seeks-plas... https://news.yahoo.com/chinese-doctors-using-plasma-therapy-161924314.html https://news.yahoo.com/chinese-doctors-using-plasma-therapy-...
- changoplatanero 7y agoWhy cant they just extract the protein from the coronavirus?
- letitgo12345 7y agoI doubt it's easy to isolate
- DrAwdeOccarim 7y agoThey can and are working on it/have already done it. The key then is to make it in large quantities. One way to avoid needing to make the protein is to deliver mRNAs for the heavy chain and light chain of the antibody. This would be faster, but it is not a proven technology so it's unlikely to work anytime soon (<1y) so convalescence treatment is much easier to do since blood transfusions are super common and well established.
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- natch 7y agoStrange site. The heading implies that they are attempting to design things that help science, but if you drill in to the pages for "new to fold.it" and FAQ, it never actually says that any of the results are used by anyone. Instead it says that it's all a game and the only science goal is to prove that humans are capable (just like computers) of doing this. I wonder if this is really all it is, or if the writers of the FAQ are just myopic about the fact that newcomers don't have the big picture, so they just forget to mention whether the results are ever used or not, or even potentially used, or even potentially looked at by anyone who might use them. Reminds me of how a lot of open source packages, when you go to their about page, just have a list of recent updates in highly technical language that assumes the reader is already familiar with the goals of the project. Sites should not assume that the reader already knows what is going on. In this case, the "new to fold.it" page is just a bunch of steps for getting started, with absolutely no overview that makes clear how any of it is all used. Under "goals" the stated science goal is just to prove that humans can solve this kind of puzzles. Really odd that teams would give time to this if it's not having any real effect though, so I suspect I'm missing something?
- astroalex 7y agoI happened to work in the lab at the University of Washington that helped maintain the game as an undergrad. Here's a published scientific article about the use of Foldit for science: https://www.nature.com/articles/nature09304 https://www.nature.com/articles/nature09304 (I'm not disagreeing that the website is badly designed.)
- natch 7y agoThanks. I’d quibble about the design word... the design is ok; it’s the wording that is lacking. Or some clear thinking. I mean for all the effort they are spending on this, it would take like one paragraph or less to clear things up. It could be fixed with five minutes of effort.
- goldenchrome 7y agoDesign encompasses everything that people interact with, so words are part of design. In fact there's a whole discipline called "User Experience Writing".
- dmd 7y agoThere's a Greg Egan short story "Zero For Conduct" that's about this kind of site.
- nednar 7y agoIf there are people with expert knowledge here, can you explain how people heal from such kind of virus (or in general) if there are no counter measures external to the infected human? I'm a little confused about how it works with virus vs bacteria.
- rolph 7y agoin short terms, the immune system does it, but it has to learn what it is first. there are "tags" on the virus, these are antigens. the immune system samples the antigens presents them to the "antibody librarian" and the librarian publishes a bunch of antibodies that stick to the virus antigen. This can take some time to get to this state, during this time the virus is replicating making you ill and doing damage. when enough antibodies are being produced, new copies of the virus will be tagged with the antibody and destroyed with haste. here is a big read with all the real [complicated] terms: https://en.wikipedia.org/wiki/Immune_system https://en.wikipedia.org/wiki/Immune_system this is basically the same process for virus, bacteria, and even some nonliving materials.
- mkchoi212 7y agoNoob question but what's the incentive behind people trying to solve puzzles on this site?? Other than glory and fame of course :p