Posts by David Baker

21) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 74200) Posted 8 Nov 2012 by David Baker Post: With your help, we have made an exciting breakthrough in protein design that is reported in a research article titled "Principles for designing ideal protein structures" in the journal Nature today. You can read about it at http://www.nature.com/news/proteins-made-to-order-1.11767 In this paper, we describe general principles for creating new proteins from scratch. The new Institute for Protein Design is using these principles to design new proteins to treat disease. Rosetta@home was absolutely critical to this work as described in the news article; Figure 3 in the paper shows how all of your contributions were used to test designed sequences to see if they folded up to the right structure. Most of the work units we are sending out on Rosetta@home these days are for exactly these kind of tests on the new proteins we are designing--this is absolutely critical to the research and to the development of new therapeutic and other functions. Thank you again for all of your contributions!
22) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 74065) Posted 21 Oct 2012 by David Baker Post: I have exciting news. We and the University of Washington are starting up a new Institute for Protein Design to design new proteins to address current challenges in medicine, energy, and other areas. You can learn more about the institute at http://depts.washington.edu/ipd/. Rosetta@home is and will continue to be a critical part of our efforts. For every new potential protein therapeutic we design, we use Rosetta@home to test whether it will actually fold into the desired structure. And we need help! We have quite a backlog of exciting new designed proteins to test on Rosetta@home because we are designing proteins for quite a range of problems-new anti flu proteins, anti-cancer proteins, and new materials--and it takes 3000-5000 work units to test each one. This Rosetta@home testing is becoming the slow step in the whole design process, often taking over 10 days to complete. So please tell your friends and relations to join us! A generous donor has provide funds which we want to use to invite 5-10 Rosetta@home participants to visit the Institute and see what we are trying to accomplish first hand. More on this in my next post.
23) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 73929) Posted 28 Sep 2012 by David Baker Post: The native structures are slowly being released for CASP10 targets; all of them will be available by the end of November. In the meantime, you can look at the results of a much larger scale test of prediction methods called CAMEO. CAMEO takes newly solved protein structure before they are published, and sends the amino acid sequences out to structure prediction servers. This happens every week, so it is great to assess new methods as they are being developed. You can look at the results, as well as get more information about CAMEO, at http://beta.cameo3d.org/modeling/weekly_summary.html The best number to compare is the "Average accuracy (all targets)" as some servers only model the easy ones. The good thing about CAMEO is that there are many more test cases than CASP, and also that results are released each week so we can see what is working well and what needs to be improved. You will see that ROBETTA, which is now using some of your computing resources, is doing pretty well recently; before this we had problems with some targets not getting enough work units before the server deadline.
24) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 73852) Posted 17 Sep 2012 by David Baker Post: The ebola work units are designing small proteins to bind to the Ebola virus. we will collect the results from all of the runs, and test those predicted to bind the virus most tightly in our experimental lab. the proteins that do bind the virus will then be tested to see if they block the virus from infecting cells. if they do, the next step is to see if they can be used as drugs to block Ebola infection. this we cannot do in my lab. a government agency could take this over for testing in a specialized lab, or the university could license to a company on the condition that the company push forward on getting the designs into the clinic as fast as possible.
25) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 73846) Posted 16 Sep 2012 by David Baker Post: All results of rosetta@home are public. as has been discussed before in these forums, the only way to actually get a potential drug into the clinic is to have a company license potential drug candidates from the university and spend the $$$ required for testing. if the company does not pursue this actively, they lose the opportunity and the university finds another company to develop the drug. as I pointed out before, this is illustrated by the fact that the Gates foundation (and other charities) will not fund projects if there is not a clear plan for companies to develop possible drug candidates that come out of it, because they know that without this the things that are discovered will never contribute to improving health.
26) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 73845) Posted 16 Sep 2012 by David Baker Post: Yes! we are now trying to design drugs that prevent Ebola from killing people-with your help hopefully we will succeed! Hi. Last days i see in queue lof of WUs from protein-protein interfaces series with names like Ebolanator3_..._ProteinInterfaceDesign_2Sep2012... It new research target? Probably connected to Ebola virus? Or it just similar name?
27) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 73800) Posted 10 Sep 2012 by David Baker Post: We are now testing the latest batch of novel designed proteins that you have helped us create in our brand new Molecular Engineering laboratory at the UW. You can see pictures of the space where the rosetta@home computed designs are being experimentally tested in a recent newspaper article: http://seattletimes.com/html/localnews/2019068219_molecularlab05m.html
28) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 73755) Posted 4 Sep 2012 by David Baker Post: A recent paper in Nature Biotechnology describes how we have combined computational protein design with the high throughput DNA sequencing methods developed for sequencing the human genome to generate potent influenza virus inhibitors. These designed proteins block infection by the flu virus in cell culture experiments, and they are now going through the (quite lengthy) process of being developed as possible anti-flu drugs.
29) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 73274) Posted 10 Jun 2012 by David Baker Post: Many common materials such as silk and wool are made out of regular repeating arrays of proteins, and symmetric protein arrays make up the coats of viruses and many other assemblies inside cells. The ability to robustly design self assembling materials made out of proteins would have huge numbers of applications-the naturally occurring assemblies are useful, but imagine if we could make custom materials for 21st century problems. In this weeks Science magazine, we describe the use of Rosetta to design self assembling protein nano structures with very high accuracy. We are now attempting to create many different types of symmetric materials, and you will be seeing more symmetric calculations on your rosetta@home screen server. Thank you for making possible this completely new approach to nanotechnology!
30) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 73020) Posted 8 May 2012 by David Baker Post: A big THANK YOU to all of you who have scaled up your contributions to Rosetta@Home-this is a record level of computing power for us and is super well timed. THANKS!!!
31) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 73000) Posted 6 May 2012 by David Baker Post: We are VERY excited about the big jump in compute power-this will make a BIG difference. Thanks to all of you!!
32) Message boards : Rosetta@home Science : CASP 10 (Message 72956) Posted 1 May 2012 by David Baker Post: Yes you are absolutely right. for CASP we need results back within a day or two, as our approach is iterative: we analyze the results after one day and send out another set of wu based on these results for two days of computing, then collect the results and submit to CASP. so please do set your buffer to a shorter time, and let us know if you are running out of wu. thanks! CASP CASP is an international experiment to assess the state-of-the-art of the protein structure prediction field. Sequences, whose structures have been solved but which have not yet been published are sent out to participating teams and we have a 3 days to send back predictions. The whole thing is conducted in a double-blind fashion ensuring fair assessment and truly blind prediction. You state you have 3 days to send back predictions. Can I ask a very specific question that I've raised before: The default work buffer set is 0.25 days with a 3 hour runtime, but some of us maintain a larger work buffer in order to avoid task outages. I personally use 2.0 days, but others may use a larger amount. The default settings allow tasks to be returned to you in good time, but is it true to say that if the work buffer+runtime totals more than 3 days, then the work we grab will not be returned to you in sufficient time for the results to count? I will assume this is the case, so I'm reducing my work-buffer to 1.5 days - plus my 8-hour runtime - to allow a certain leeway for you to receive work back in time. Please confirm so that others can make similar adjustments. Obviously, with reduced work buffers, there's an equivalent requirement for tasks to be reliably available at your end, so an extra degree of monitoring would be wise. On the assumption that my guesses are correct, you may see a reduced rate of task downloads while our buffers are run-down, though tasks wil be returned a certain amount sooner after release. As long as tasks are readily available there should be no reduction in results you see back.
33) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 72930) Posted 29 Apr 2012 by David Baker Post: I have just been told the very good news that Rosetta@home will be the first project of the BOINC pentathlon, and would like to thank all of the participating teams. I also just learned from the discussion thread that Rosetta@home will be the project of the month for BOINC synergy-this is more excellent news!! Your increased contributions to rosetta@home could not come at a better time! We've been testing our improved structure prediction methodology in a recently started challenge called CAMEO. For most of the targets, the Rosetta@home models are extremely good, but for a minority of targets the predictions are not good at all. We've now tracked down the source of these failures and it is what we are calling "workunit starvation"; in the limited amount of time the Rosetta server has to produce models (2-3 days) in these cases very few models were made-this happens because many targets are being run on the server so that only a fraction of your cpu power is focused on any one target. while we are working to fix this internally, by far the best solution is to have more total CPU throughput so each target gets more models. You can follow how we are doing at http://www.cameo3d.org/. You will see that Robetta is one of the few servers whose name is not kept secret-this is because Rosetta is a public project. Our server receives targets from CAMEO and soon CASP, sends the required calculations out to your computers through Rosetta@home, and then processes the returned results and submits the lowest energy models. We are excited that the workunit starvation problem may go away through your increased efforts for Rosetta@home. Thanks!!!
34) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 72929) Posted 29 Apr 2012 by David Baker Post: BOINC Synergy based in Australia but with members all over just voted to make Rosetta Project of the Month for May 2012! Hope that helps with CASP 10! Yes it will help tremendously-thanks!!
35) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 72699) Posted 8 Apr 2012 by David Baker Post: I've described in the past our work using Rosetta and Rosetta@Home to create new enzyme catalysts. In Nature Chemical Biology last month we describe the design of an enzyme which destroys organophosphate nerve agents and pesticides. These compounds kill by blocking key enzymes, and our designed enzyme eliminates this toxicity. This illustrates how Rosetta@Home enzyme design work can help to solve current problems, including man-made problems.
36) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 72698) Posted 8 Apr 2012 by David Baker Post: I apologize for the lack of feedback; we are all really busy with the research-but this is no excuse. I've asked the scientists using rosetta@home in my group to each open a new thread describing the problem they are working on, intermediate results, etc so hopefully you will be getting a lot of feedback soon!
37) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 72628) Posted 30 Mar 2012 by David Baker Post: In the last two months we believe we have made quite a breakthrough in structure prediction, and are excited to test the new method in CASP10. We need your help though--we are now testing many aspects of the new approach and are seriously limited by available CPU cycles. There are now so many flu inhibitor design and structure prediction jobs queued up on Rosetta@Home that there is an eight day wait before they are getting sent out to you. This would be a great time to temporarily increase Rosetta@Home's share on your computers and/or recruit new users--we need all the help we can get! thanks! David
38) Message boards : Rosetta@home Science : DISCUSSION of Rosetta@home Journal (5) (Message 72289) Posted 13 Feb 2012 by David Baker Post: That's great news! Is there any mileage in running the FoldIt enzyme on Rosetta? It sounds like brute force (i.e. R@H) is good for evolution and FoldIt for revolution (kinda like punctuated evolution in nature) - does that seem correct? I belive that is what Dr. Baker means when he says that the combination of the two is very powerful. As you say, the human Fold.it player is more likely to find revolutionary or intuitive designs, and then Rosetta@home can be used to further refine them and further explore the area around the new design idea. Yes I think this is a good way to look at it. We are still trying to understand when and how to use FoldIt to get new ideas on how to approach a problem. One area we are focused on now is to design inhibitors to flu strains our existing designs don't already inhibit. we've been using Rosetta@home extensively for this and have some very promising designs we will soon be testing. but we have the feeling that there are other possible ways to tackle the problem, and to explore these we will be releasing soon a set of FoldIt puzzles aimed at identifying other ways to grab onto the virus surface.
39) Message boards : Rosetta@home Science : David Baker's Rosetta@home journal (Message 72230) Posted 29 Jan 2012 by David Baker Post: Last year we described in Science magazine the design of a new enzyme which catalyzes a chemical reaction called the Diels Alder reaction involving the formation of two carbon-carbon bonds. This reaction is interesting because no natural enzymes are known to catalyze the reaction. However, it wasn't a very good enzyme, and we asked FoldIt players to try to improve it. As described in Nature Biotechnology this month, remarkably FoldIt players were able to make the designed enzyme 20 times faster by inserting a completely new loop which helps the enzyme bind the chemicals it links together. The combination of Rosetta@Home and FoldIt is turning out to be powerful indeed for solving challenging problems in biomedicine!
40) Message boards : Rosetta@home Science : Design of protein-protein interfaces (Message 72184) Posted 20 Jan 2012 by David Baker Post: The projects that James is working on that he has described below all involve targeting proteins that are on the inside of the cell. the projects we are just beginning target proteins on the outside of cancer cells. since the rosetta@home methods allow in principle the design of tighly binding proteins to any target, we have a lot to do!

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