Jump to content
PcPerf.fr

PcPerf bot

PcPerfonaute
  • Content Count

    378
  • Joined

  • Last visited

Everything posted by PcPerf bot

  1. Understanding protein folding has many possible areas of biological and biomedical impact. For example, consider one of the major research areas of the Kasson lab at the University of Virginia, namely how the influenza virus infects cells. In the past, Dr. Kasson and Dr. Pande have studied two aspects of this: how the influenza virus recognizes cell-surface receptors so it infects the "right" cell types and how small vesicles fuse. Dr. Kasson's group is now looking at the function of the viral protein that controls cell entry, a protein called hemagglutinin. The hemagglutinin protein interacts with cell membranes: one piece inserts into the membrane, refolds, and alters the membrane in some unknown manner to promote viral entry. Another piece links the viral and cell membranes and refolds to bring the two together. We are running simulations on Folding@Home to examine each of these pieces. Dr. Kasson's laboratory also looks at these processes experimentally. Both of these problems involve protein folding. This extends the problem of understanding folding beyond the "canonical" model of an unstructured protein in water taking on a final shape but instead in the first case a small protein inserting into a lipid membrane and changing shape in response to its environment and in the second case a large protein changing from one shape to another in response to physiological cues. One could consider these special cases of protein folding or how viruses use protein folding to infect cells. Future posts will address methods we have developed to assist in these studies as well as other important problems we work on. We are also doing methodological work that will improve the efficiency of running Folding@Home simulations and analyzing the results. The Folding@home community has made an important contribution in providing the computing power for these studies (you can see some of our published work on the FAH papers page), and we are grateful to all involved. Voir l'article complet
  2. The FCF site has had some DNS changes and you may not be able to reach it from its normal url (http://foldingforum.org/). If not, please try this one temporarily: http://m202.sgded.com/~folding1/ Voir l'article complet
  3. Here's a guest post from Prof. Xuhui Huang's lab at Hong Kong University of Science and Technology, another collaborating labortory in the Folding@home consortium. Prof. Huang and his lab have made several important methodological applications to FAH (for more details, see this review article) as well as important research into the molecular nature of Huntington's Disease. Here's an update from Prof. Huang: In the past a couple of years, the FAH has greatly helped us on our research on understanding the mechanisms of the molecular recognition processes. Molecular recognition, such as enzymes need to recognize their substrates and drugs have to be designed to specifically bind to certain receptors, is crucial to biology and medicine. Experimentally probing the chemical details of molecular recognition events is challenging, while computer simulations have the potential to provide a detailed picture of such events. With the help of the FAH donors, we are performing large-scale simulations on a group of Periplasmic Binding Proteins aiming to reveal the general relationships between protein structures, its intrinsic dynamics, and mechanism of recognition process. The FAH projects related to the above research are between 7700 and 7712. We greatly appreciate the help from all the FAH donors, beta testers, and the rest of the FAH team to make our research on molecular recognition possible. Voir l'article complet
  4. Here's a guest post from Prof. Xuhui Huang's lab at Hong Kong University of Science and Technology, another collaborating labortory in the Folding@home consortium. Prof. Huang and his lab have made several important methodological applications to FAH (for more details, see this review article) as well as important research into the molecular nature of Huntington's Disease. Here's an update from Prof. Huang: In the past a couple of years, the FAH has greatly helped us on our research on understanding the mechanisms of the molecular recognition processes. Molecular recognition, such as enzymes need to recognize their substrates and drugs have to be designed to specifically bind to certain receptors, is crucial to biology and medicine. Experimentally probing the chemical details of molecular recognition events is challenging, while computer simulations have the potential to provide a detailed picture of such events. With the help of the FAH donors, we are performing large-scale simulations on a group of Periplasmic Binding Proteins aiming to reveal the general relationships between protein structures, its intrinsic dynamics, and mechanism of recognition process. The FAH projects related to the above research are between 7700 and 7712. We greatly appreciate the help from all the FAH donors, beta testers, and the rest of the FAH team to make our research on molecular recognition possible. Voir l'article complet
  5. Here's an update one one of our key projects looking into protein folding, performed in collaboration with Prof. Jesus Izaguirre's lab at Notre Dame. Below is an update from Prof. Izaguirre on the progress of this project. The Izaguirre Lab at the University of Notre Dame (http://www.nd.edu/~lcls) has been collaborating with the Pande Lab at Notre Dame to produce a new GPU core that leverages the amazing speed of OpenMM implicit-solvent force calculations (the heart of the GPU core in Folding@home) with new Long Timestep Molecular Dynamics (LTMD). This combination currently allows nearly a 10-fold speedup over OpenMM for systems as small as the WW domain (35 residues, 544 atoms) up to the Lambda repressor (80 residues, 2000 atoms). This translates into about 10 microseconds per day of simulation, which brings single trajectory millisecond simulations closer to FAH. In collaboration with Cauldron Development (lead by Joseph Coffland, primary developer of the Folding@home client and also some cores), we hope to produce a GPU core that might be the first hybrid CPU-GPU core. There are technical questions on how to best do this, and we will engage our enthusiastic beta-tester GPU donors to discuss how to best approach this core when we are closer to production mode. Going forward, we will continue to improve the LTMD GPU technology to obtain larger speedups for ever larger and biomedically relevant systems. A particularly excitement development will be the extension of LTMD GPU technology to explicit solvent simulations. As far as scientific simulations, we are simulating the folding of about 80 mutants of the Pin1 WW domain, a protein implicated in some cancers and Alzheimer's disease. Understanding the role of mutations on misfolding can have important biomedical consequences, since many diseases have at least some component of misfolding of proteins. Another exciting project we are about to start is to simulate the dimerization during folding of proinsulin and proinsulin mutants, which results in some types of Type IA young and adult onset diabetes. Thanks to the FAH donors, testers, and to the Pande Lab for their generosity and leadership which has allowed our technological developments and simulations to come this far. An image of the Pin WW domain. Voir l'article complet
  6. The stats system went down last night and is now back up. We are working on recrediting the WUs that came in last night. WUs coming in now should be getting credit as always. Voir l'article complet
  7. As we've mentioned earlier, we have been preparing changes to the bigadv system –– both an increase in the number of cores required (and a shortening of deadlines to match) and the release of some new bigadv projects. The motivation for the core changes is as follows: Bigadv is intentionally intended for the most powerful machines, which makes it naturally a moving target. Our goal with bigadv is to utilize the most powerful segment of (CPU-based) machines in the FAH project to work on projects that are particularly large (memory utilization, upload/download requirement) and require a large amount of computation. We are all fortunate in that processors get faster over time, so the highest-performing tier of donor machines also gets faster over time. We have a lot of exciting science being enabled by FAH donors, and it takes place at all levels of computational requirement and performance sensitivity. So it wouldn't help the project to have 50% of machines running bigadv. But it also wouldn't be a good match to have some of the older and/or bandwidth-limited machines running these most performance-sensitive projects. As previously announced, our plan is to shorten the deadlines of the BA projects. As a result, assignments will have a 16 core minimum. We've been developing the new projects for the new "bigadv-16". This development has taken a bit longer than we expected, but we are now completing internal testing and reading beta projects for bigadv-16. We are bringing a new server online for bigadv-16. It will start by offering a new class of bigadv projects, but we will soon add in a number of projects on the same server that are more similar to bigadv projects donors have already seen. We want to make these work units available for testing, but at the same time we are still examining the points yield of these bigadv projects. So the points valuation remains a work in progress; we may alter points, bonuses, and/or deadlines in the process of testing. Please expect a beta announcement soon for testing these new bigadv-16 work units. Then, after the new bigadv-16 projects stabilize, we will bring the bigadv-12 projects into line (points, deadlines) with the bigadv-16 projects and convert all projects to bigadv-16. We are not sure of the timescale for this yet, as we'd like to test the new projects in a thorough manner. We will endeavor to be as transparent as we can regarding upcoming changes in the bigadv program. Bigadv-8 projects will likely be phased out (and indeed are mostly not being assigned at this time). As a side note, we recognize that the number of cores is a somewhat crude measure for system performance. Long-term, we have some ideas on how we'd like to improve this and use better metrics. But in the near term, we are using this admittedly imperfect metric. Thank you for folding and for your support of the bigadv program and FAH more generally. Voir l'article complet
  8. We've finished our stats recredit. It should be comprehensive, but we encourage donors to let us know in our forum if there are still problems. Voir l'article complet
  9. We're investigating reports that donors stats were not registered into the stats system. We're working on a recredit now. Voir l'article complet
  10. Here's our (I think) last update on this recent outage. This was a major disaster at Stanford affecting the whole campus and I'm grateful for our team coming in on Sunday to get things back up. The workservers have been up since then and work and stats have been saved. The stats updating was put on hold until we can make sure everything looked ok. We've turned it back on. Please note that there is no stats loss while we turn off updates. People should see a big bump in their stats shortly. Thanks for bearing with us through this. Voir l'article complet
  11. The whole Stanford campus is having a major issue due to the lack of chilled water on campus. This is causing issues for many of our servers in different server rooms. As of this moment, this is still not resolved. We cannot bring servers back on line until this is resolved. It's getting late (~10:30pm PST), so we'll check back tomorrow morning to see hopefully that this is resolved. Until then, several of FAH's servers are down unfortunately. UPDATE 4:30am Pacific Time: Chilled water came back on line at 11pm, but several of our servers are still down. Our sysadmins will work to get them back up, but it may not be until Monday, depending on their availability on Sunday. UPDATE 11:30am Pacific time: Our sysadmins have been in the office getting machines back on line. We're almost there, although it looks like there are a few machines which have issues resulting from the outage. Voir l'article complet
  12. We have a network issue at Stanford in one of our data centers. We are working on it now. Update: Everything is back up now. Voir l'article complet
  13. We just received notice that the School of Medicine has scheduled an emergency network downtime Tonight between 5-6 pm (pacific time). Network engineers expect end users to experience a single, 30-60 second network disruption as part of their work, but I'm posting this in case there's something more significant. Voir l'article complet
  14. Several of the FAH servers are located at Stanford Medical School. The Stanford School of Medicine Networks have reported outages last night (Thursday, Nov 17, 7:50-9:18 pm, pacific time) and this morning (Friday, Nov 18, 7:47 am, pacific time). Stanford IT is working with the vendor to diagnose the source of the problems. We have been warned that the medical school network may possibly be unstable today. However, note that many of the servers at Stanford are not on this network and moreover we have redundant systems (eg redundant assignments servers) not on this network, so work should go smoothly. There may be delays in updating stats however. Hopefully this is a resolved issue, but we are monitoring the situation in case it isn't. Voir l'article complet
  15. The Stanford News Service recently came by to do a video for Folding@home. Here it is: Voir l'article complet
  16. Big Advanced (BA) is an experimental type of Folding@home WUs intended for the most powerful machines in FAH. However, as time goes on, technology advances, and the characteristics associated with the most powerful machines changes. Due to these advances in hardware capabilities, we will need to periodically change the BA minimum requirements. Thus, we are shortening the deadlines of the BA projects. As a result, assignments will have a 16 core minimum. To give donors some advance warning, we are announcing this now, but the change will take place in 2 months: no earlier than on Monday January 16, 2012. We understand that any changes to how FAH works is a disruption for donors, and we have been trying to minimize such changes. For that reason, we are not changing the points system at this time. However, we want to emphasize that the BA program is experimental and that donors should expect changes in the future, potentially without a lot of notice (although we will try our best to give as much notice as we can). In particular, as hardware evolves, it is expected that we will need to change the nature of the BA WUs again in the future. Voir l'article complet
  17. We've been working to make the behind the scenes tasks of Folding@home better communicated with FAH donors. In the last few months, there have been many recent changes, including making the beta team forum open and making our v7 client bug tracker open for all to read. Today, I wanted to talk about another experimental change, the formation of a Donor Advisory Board (DAB). We've in the past gotten lots of feedback from donors on our Forum site (http://foldingforum.org). Based on discussions with many donors, we have been working to expand these discussions to a broader group of donors and have formed a Donor Advisory Board. The DAB is currently comprised of: rjbelans (folding@evga), kendrak ([H]ardOCP), zodac (Overclock.net), ChasR (www.overclockers.com), and Michael McCord (MaximumPC), Bruce Borden (Forum Admin), and myself. The goal of the DAB is to improve communication in both directions and so far I think it's been helpful in that regard. Pasted below is the first set of agenda items that we have been working on. 1) Improving communication: What can PG do to help improve communication? 2) Beta testing plan: How to improve transparency without lowering the quality of beta testing. 3) Points consistency: How to make PPD more consistent. We've made changes in all three areas but none of these can be considered "done". My hope is that the DAB will help feedback in both directions, giving us broader perspectives of donors concerns and also to better communicate what we're doing to improve FAH and push towards greater scientific achievements. Voir l'article complet
  18. We've been getting reports that donors can't get SMP WU's. There are plenty of SMP WUs, but they require client v6.34 (or later). The servers that can handle the older SMP client (v6.29 or later) are running low on WUs, but there are plenty of WUs for the newer clients. If you're not getting WUs, please consider upgrading your client. You can download it here: http://folding.stanford.edu/English/DownloadWinOther Moreover, it's a good time to try out the beta version of our new v7 client! https://fah-web.stanford.edu/projects/FAHClient/wiki/BetaRelease Voir l'article complet
  19. Right now, the two most powerful supercomputers for studying protein folding are Folding@home and a very impressive special purpose computer from DE Shaw Researched, called ANTON. We're often been asked "how do they compare?" The approaches are very different, so comparisons aren't completely straightforward. ANTON takes the traditional approach to studying protein folding, where one performs a few (often 1 or 2) long trajectories to study the process. Folding@home takes a statistical approach, which has two primary benefits: 1) it can access folding on dramatically longer timescales (milliseconds, instead of microsecond folding events over a single long trajectory) and 2) it can give statistically significant results on those long timescales. The main concern about the method in FAH is that since it is such a radically new approach, does it work reliably? Previous tests of FAH have been to experiment, which is the gold standard test, but also brings in other issues, such as how good are our models of reality. Thus, while FAH's approach has done well compared to experiment, it is useful to compare FAH and ANTON directly, since they use the same models, etc. Comparison of our statistical approach (using Markov State Models, aka MSMs) directly with data from ANTON would go a long way to showing that the MSM approach works for even non-trivial systems (they have been previously tested for long dynamics on small systems). In a recently published paper, we make this comparison. By applying MSMs to data from ANTON, we find that FAH's approach (MSMs) can reproduce the long timescales in ANTON data very well. Moreover, we also find that the MSM approach can find important new features missing in the more traditional analysis approach originally applied to the ANTON data, relevant for understanding folding and function. For us, this is exciting since it shows the capabilities of the MSM method. However, I want to stress that perhaps the most exciting part is how ANTON and FAH could be used together. A run on ANTON followed by more thorough sampling in Folding@home could be the best of both worlds. PS Here's the abstract for our paper (http://pubs.acs.org/doi/abs/10.1021/ja207470h?prevSearch=lane%2Bpande&searchHistoryKey=): Two strategies have been recently employed to push molecular simulation to long, biologically relevant timescales: projection-based analysis of results from specialized hardware producing a small number of ultra-long trajectories and the statistical interpretation of massive parallel sampling performed with Markov state models (MSMs). Here, we assess the MSM as an analysis method by constructing a Markov model from ultra-long trajectories, specifically two previously reported 100 µs trajectories of the FiP35 WW domain (Shaw et. al. (2010) Science, 330: 341-346). We find that the MSM approach yields novel insights. It discovers new statistically significant folding pathways, in which either beta-hairpin of the WW domain can form first. The rates of this process approach experimental values in a direct quantitative comparison (timescales of 5.0 µs and 100 ns), within a factor of ~2. Finally, the hub-like topology of the MSM and identification of a holo conformation predicts how WW domains may function through a conformational selection mechanism Voir l'article complet
  20. We've released the latest v7 client (7.1.38) in our forum. I've pasted the update from Joseph Coffland (lead programmer), outlining the progress so far. Documentation Installation and user guides can be found here: FAHControl -> The Graphical User Interface (GUI) what controls the Slots. FAHViewer -> It shows the protein being folded, if applicable. Pictorial Installation Guide (Windows) -> A detailed pictorial guide on the V7 installation. Installation Guide (Windows) -> A brief guide on Windows installation. Installation Guide (Linux) -> A guide for Linux installation. Installation Guide (OSX) -> A guide for OSX installation that is in progress. Client Remote Interface -> Documentation for 3rd party developers. Main Page -> Main page of the V7. Getting Help Aside from the documentation the best place to get help is in this forum. If you do have a problem post a message. There are many knowledgeable people ready and willing to help. Keep in mind, we greatly appreciate thorough reports delivered by patient people who can keep a cool head even when things go wrong. Bugs/Tickets Open Tickets Ordered by Milestone and Priority Active Tickets by Change Time Note: Some tickets may be closed because they are fixed in an upcoming alpha release but are not yet fixed in the beta release. _______________________________________________________________________________________ Beta Testers, I've been focusing on addressing the issues which most affect v7 client users and which may help those still running v6 clients to make the decision to upgrade to v7. Your feedback has been very important, not only in finding and solving bugs but in prioritizing development time. One donor had these concerns with using v7.1.33: Jesse_V wrote:I'd be happy to try out v7.1.33 and its upgrades if I was confident that my participation wouldn't hurt science. I am concerned with a number of bugs in v7, things such as FAHClient taking up way too much CPU time and slowing things down. I also am concerned about v7 not being able to talk to the servers right, especially when errors occur. Although the issues Jesse_V mentioned only affected a small portion of the v7 users they were legitimate concerns. I made sure these issues were thoroughly addressed in this release. Concerns like this are exactly what we need to hear about. If you are also concerned about v7 affecting the science of Folding@home I have this to say. v7 is more likely to increase your contribution but if you do have a problem, and you report it, you are potentially helping thousands of users donate computing time to Folding@home so it's more likely a net gain. However, beta testers often have to be satisfied with peer recognition and praise rather than points. If you've been on the fence about v7 now is a great time to upgrade. Here are some of the other comments we've been getting: jimerickson wrote:i am running windows 7 ultimate 64bit and windows 8 developer preview release. everything went smoothly. . .keep up the excellent work. DarkFoss wrote:The upgrade from v7.1.24 to 7.1.33 went flawlessly. . .install took less than a minute and it resumed folding the wu's they finished without issue. . . OEOTS wrote:Congrats on the new release guys. with V7 you've made it all so much easier. soya_crack wrote:Wow, that is one of a big advance. That was what F@H just needed. It's awesome. Easy to understand and just kickin' ass, the slot thing is what I was missing from BOINC. WhiteLion wrote:Awesome! The best client i ever use, perfect for newbies, easy setup. . . There are still several issues that need to be addressed before we go to the front page with the v7 client. Specifically the tickets listed in Milestone Open Beta Phase 2 under ticket report 3. Log filtering (#157), better ETA calculation (#395) and better handling of cores that don't terminate cleanly (#563) are the top three items. There is more work to do but we are getting ever closer to a front page release of the v7 client. Thanks for all your bug reports and feedback. Keep telling us what issues are most important to you and we will do our best to address them. Joseph Coffland Folding@home Developer Cauldron Development LLC Documentation Installation and user guides can be found here: FAHControl -> The Graphical User Interface (GUI) what controls the Slots. FAHViewer -> It shows the protein being folded, if applicable. Pictorial Installation Guide (Windows) -> A detailed pictorial guide on the V7 installation. Installation Guide (Windows) -> A brief guide on Windows installation. Installation Guide (Linux) -> A guide for Linux installation. Installation Guide (OSX) -> A guide for OSX installation that is in progress. Client Remote Interface -> Documentation for 3rd party developers. Main Page -> Main page of the V7. Getting Help Aside from the documentation the best place to get help is in this forum. If you do have a problem post a message. There are many knowledgeable people ready and willing to help. Keep in mind, we greatly appreciate thorough reports delivered by patient people who can keep a cool head even when things go wrong. Bugs/Tickets Open Tickets Ordered by Milestone and Priority Active Tickets by Change Time Note: Some tickets may be closed because they are fixed in an upcoming alpha release but are not yet fixed in the beta release. Here are the change logs: v7.1.38: Fixed network connection dropping. v7.1.37: Added missing wraplabel.py file to FAHControl. Changed socket error message verbosity. Fail WU on UNSTABLE_MACHINE immediately & return for partial credit. #615 v7.1.36: Fixed a potential socket connection bug. Maybe related to #734. Added several NVidia cards to GPUs.txt. #737. Improved Linux on battery detection. #738. Print WU error state on WU status line. Emit correct exception on FAH transaction failure. #615. Fixed debian package install core permissions problem. #732. Removed core byte order warning. #602. Added GPL link to FAHControl about. #736. Ask user, team, passkey and mode during .deb package install. #739. v7.1.35: Added 'Enchanter' theme. #731 Renamed 'Wimp' to 'Windows-Default'. #731 Unminimize FAHControl window on unhide. #567 Better core download failure message. #161 Cleaned up project descriptions using html2text.py. Store project data in client DB. Use system default font size. #733 Added project info to viewer. #575. Added clickable buttons to viewer. Fixed FAHViewer crash introduced in v7.1.34. Fixed mouse wheel scrolling in FAHControl. #463. Fixed color difference for text boxes. #698. Changed FAHControl window name. #711. v7.1.34: Fixed CPU consumption in client connections. #702 Really fixed "Wrong architecture" bug on 32-bit Ubuntu. #599 Only warn on config errors. #722 Log error and continue of command server fails to initialize. Fixed Slot configuration text. #717 Use -1 or 0 for CPUs default to be consistent with GPU options. #717 Disabled no longer supported AMD X1300 - 1900 GPUs. Added "OpenGL Render" to info in FAHViewer. (For blacklisting) Added 'override-blacklist' option to FAHViewer. (Nothing black listed yet) 'OK' -> 'Save' in FAHViewer preferences window. #724 Fixed NVIDIA_DEV.1244.01 = "NVIDIA GeForce GTX 550 Ti" detection. Added the 'Wimp' theme and win32 theme engines. #723 Made 'Wimp' theme the default in Windows. #713 Added heartbeat to viewer<->client connection to timeouts dead connections. Stop trying FAILED, FAULTY and DUMP reports if WS connection was made. #728 Check WS server versions for unreasonable values. #728. Here are the highlights and some of the technical details of the changes in this open-beta: Improved network handling: A number of networking related issues were solved. The run away CPU usage problem was caused by incorrectly handling dropped connections. Periodic connection loss on Windows machines was caused by not correctly handing a quirk in the Windows sockets API which was the cause of the greyed out FAHControl that some people were experiencing. Also, dropped connections are now being cleared out of the client much more quickly. This keeps dead connections from accumulating which caused problems in a few cases. Improved communication with older WS: Several problems with communication with older WS were fixed. This version does a better job of detecting older WS and aborts the error loops that the previous client got into when incorrectly trying to upload DUMP reports to the old servers. This was the cause of the repeated upload errors many people saw in their logs. Also, a bug was fixed in the handling of UNSTABLE_MACHINE core return code which was the start of many of these DUMP communication loops. GPU detection: More cards were added to the whitelist and some older, no longer supported, GPUs were removed. Debian package improvements: A permissions problem was fixed that was causing WU loss after reinstall. The installer also now asks for user, team and passkey if /etc/fahclient/config.xml does not already exist. RPMs and OSX packages still need this feature. Added a native Windows theme (Wimp): The Wimp (Windows Implementation) theme was added to FAHControl. This theme gives a true native look on all Windows platforms because the theme engine actually uses the Windows system to render the GUI components. This is now the default theme for Windows platforms. Still need something like this for OSX. Voir l'article complet
  21. I filmed a new interview about Folding@home, which gives some potentially interesting details about FAH especially for those who are new to the project. The show is Futures in Biotech 85: Modeling Life With The World's Most Powerful Computer System. Dr. Vijay Pande, Stanford's Director of Folding@home, details how the World's most powerful system models Alzheimer's and other human diseases. Voir l'article complet
  22. I have some good news. Due in large part to the work we've done with Folding@home, I've been named the recipient of the 2012 Michael and Kate Bárány Award for Young Investigators from the Biophysical Society for "developing field-defining and field-changing computational methods to produce leading theoretical models for protein and RNA folding." This was just annouced in the Biophysics Society newsletter and their web site hasn't been updated just yet for the 2012 awards. As with all of the accolades coming to our work, this is very much a team effort, and I'm excited that our collective work is being well-recognized. Voir l'article complet
  23. We have made a major update to the Results page on the Folding@home web site. We now list 95 papers that have directly resulted from Folding@home, although we note that there are 193 papers from the Pande group in general. There are many new results to talk about, but I will just highlight a few below. One major result is in the area of Alzheimer's Disease (paper #95). It is believed that Alzheimer's Disease results from the misfolding of the Abeta peptide. Understanding how Abeta misfolds could give us some key insights into how to cure Alzheimer's Disease. This paper experimentally tests a key prediction made in an earlier paper (paper #58: "Simulating oligomerization at experimental concentrations and long timescales: A Markov state model approach" by Nicholas W. Kelley, V. Vishal, Grant A. Krafft, and Vijay S. Pande. J. Chem. Phys. 129, 214707 (2008); DOI:10.1063/1.3010881). In this paper, we show experimentally that there appears to be a beta turn in the Abeta as predicted. This leads to a very stable form of misfolded Abeta which could be used as a starting point for a new Alzheimer's therapy. We are heavily pursuing this research direction at the moment. Another key result is in the area of methods (paper #93). We are constantly honing our methods to improve Folding@home's ability to predict the behavior of proteins. This paper demonstrates the current state of the art in terms of both sampling and analysis. When compared to detailed TTET experiments, we show that our methods can piece out even fairly detailed aspects of folding. However, we also see the ways in which our models are not perfect, suggesting how we can improve our methods even further. We'll highlight other papers as time goes on. I'm particuarly excited about these results. In particular, the results from paper #95 were first discovered several years ago, but we carried out several followup studies to verify them, etc. As always, I'm most excited about what we're doing now and hope to get some of our current key results in theses areas out from peer review soon. Voir l'article complet
  24. We've developed a new serverstat page, which we're now suggesting as a replacement for the old one. The new one is more asthetically pleasing but also has a lot of changes under the hood to allow for more reliable and faster updates. We're keeping the old serverstat page link pointing to the old page (i.e. no change) in case there were scripts that were parsing the old page. However, we've set the new page to update every 10 minutes and the old one to only update every hour. We will keep the old page up for at least two months to give 3rd party utilities a chance to update their code and to give us feedback (please post feedback to http://foldingforum.org ). Voir l'article complet
  25. For new bigadv WUs, we have changed how the points are calculated to bring them back into balance with the rest of the points in Folding@home. There are more details in this post: http://foldingforum.org/viewtopic.php?f=24&t=19059 The main jist of the change is that we are decreasing the points associated with bigadv WUs, from 50% over SMP to 20% over SMP. As with previous points changes, this deals with only new WUs to go out, not with WUs that have be collected, etc. I want to stress that the bigadv program is still continuing, but that, as we've mentioned before, this is an experimental program and subject to changes. It's clear that any change to the points system is controversial, but this one has been raised as a very serious problem by many donors. After investigating the issues raised, we agreed that this was significantly out of balance, and made this change. Moreover, the feedback we have gotten is that we make a change soon and do so quickly, like "removing a bandaid" rather than drag out the pain. I'm sorry to have to make any changes at all, since any change is disruptive, but we (and many donors) felt very strongly that this change was very important. The other change that we have in mind to do is to bring all classic and GPU WUs into the Quick Return Bonus (QRB) system. This would help further bring all FAH projects into balance. There may be some issues with GPUs and QRB, so we are looking to see what we can do to minimize problems with that before making a change in the points for GPU WUs. Finally, I would like to remind all that we do listen to donors and take their input very seriously. There has been extensive discussions about the problems with the points system with the huge PPD's seen with bigadv (sometimes reaching 500,000PPD) and the lack of QRB for GPUs being major shortcommings. Considering the great variety of donor opinions on this matter, it is no surprise that we agree with some donors and disagree with others. Moreover, with points, there will never be any system which makes everyone happy, but our goal is to try our best to balance the project as a whole, taking donor input seriously, and making hard calls when we feel it is necessary. This was definitely a hard call, but hopefully in time donors who disgaree now will come to understand the issues raised by the other donors and appreciate their point of view. Voir l'article complet
×
×
  • Create New...