F@H Updates

[iancook221188]

From the Official FAH Blog:
http://folding**************/

Bonus for A4-core based projects –– now in effect

A brief update to our previous blog post on the A4 bonus: the bonus is now in effect.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

July 23, 2012
Searching for new drug targets

Guest post from Dr. Gregory Bowman, UC Berkeley

Most rational drug design efforts assume the target protein exists in a single structure and that the structure of one region of the protein--called the active site--allows the protein to perform some function. Once this assumption is made, the only way to manipulate a protein’s activity is with inhibitors that bind the active site tightly enough to block it from performing its intended function. Unfortunately, this strategy only works for ~15% of proteins, greatly limiting the number of proteins we can manipulate for therapeutic purposes.

In a recent article published in the Proceedings of the National Academy of Sciences (link), I showed that simulations run on Folding@home can reveal new ways of manipulating a protein's activity. Specifically, I start off by recognizing that proteins are actually flexible and then use Folding@home to enumerate the different conformations a protein adopts. I then use statistical analysis to find parts of the protein that can communicate with the active site through a process called allostery. These regions--called allosteric sites--are attractive drug targets as the binding of small molecules to them can be communicated to the active site, ultimately affecting activity.

As a proof of principle, I showed that my approach can identify a known allosteric site in Beta-lactamase (see figure below). This protein is an important drug target because it can confer bacteria with antibiotic resistance by breaking down antibiotics like penicillin. I also use my approach to predict new allosteric sites in Beta-lactamase and two other proteins that play important roles in immune deficiencies and HIV. Now I'm performing experiments to test my predictions. It will require a lot more of your WUs, but I hope this type of approach can eventually lead to new pharmaceuticals.



On the left is a structure of Beta-lactamase that most people would think of as the structure of this protein. However, the right shows a different structure with a drug (cyan) bound in a pocket that isn’t visible in the structure on the left. Binding of this drug somehow affects the structure near the active site (green). Using my approach, I’m able to start with the structure on the left and then predict the existence of the structure on the right and the allosteric site the drug is bound to.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

August 20, 2012
MSMBuilder: Open source code from the FAH developer community

Guest post from Dr. Gregory Bowman, UC Berkeley

We’ve been making a lot of progress with developing Markov state model (MSM) methods for analyzing the data we generate with the help of the FAH community. For those of you with a theory background, MSMs are just discrete-time master equation models. For everyone else, MSMs are a way of describing the conformational space a protein (or other biomolecule for that matter) explores as a set of states (i.e. distinct structures) and the transition rates between them. Much of the theory underlying these methods is quite old but their use has been limited by the challenges inherent to identifying a reasonable set of states.

During my time in the Pande lab, I worked with Xuhui Huang (now at the Hong Kong University of Science and Technology) to develop new methods for building MSMs from the large data sets we generate with FAH. Together, we started an open source software package called MSMBuilder (here) to automate the process of building MSMs. Now a number of more recent additions to the Pande lab are helping Xuhui, Vijay, and me in continuing to develop the software.

As we just released an update to MSMBuilder, I was looking back at some of our user statistics and was pleased to see how quickly our project is gaining traction. Since its initial release in 2009, there have been over 1,600 unique downloads of MSMBuilder. One cute feature of our webpage—provided by the SimTk software consortium at Stanford—is that you can go look where all of our users are (here). Its fun to see that MSMBuilder is being used on 5 continents. Maybe most importantly, MSMBuilder has been used in at least 40 publications to date. MSMBuilder is coming up at conferences with increasing frequency too, so I look forward to reporting back on our growth in another year or so.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

September 10, 2012
New methods for analyzing FAH data

Guest post from Dr. Gregory Bowman, UC Berkeley

Two general objectives of the Folding@home project are (1) to explain the molecular origins of existing experimental data and (2) to provide new insights that will inspire the next generation of cutting edge experiments. We have made tremendous progress in both areas, but particularly in the first area. Obtaining new insight is even more of an art and, therefore, less automatable.

To help facilitate new insights, I recently developed a Bayesian algorithm for coarse-graining our models. To explain, when we are studying some process—like the folding of a particular protein—we typically start by drawing on the computing resources you share with us to run extensive simulations of the process. Next, we build a Markov model from this data. As I’ve explained previously, these models are something like maps of the conformational space a protein explores. Specifically, they enumerate conformations the protein can adopt, how likely the protein is to form each of these structures, and how long it takes to morph from one structure to another. Typically, our initial models have tens of thousands of parameters and are capable of capturing fine details of the process at hand. Such models are superb for making a connection with experiments because we can capture all the little details that contribute to particular experimental observations. However, they are extremely hard to understand. Therefore, it is to our advantage to coarse-grain them. That is, we attempt to build a model with very few parameters that is as close as possible to the original, complicated model. If done properly, the new model can capture the essence of the phenomenon in a way that is easier for us to wrap our minds around. Based on the understanding this new model provides, we can start to generate new hypotheses and then test them with our more complicated models and, ultimately, via experiment.

Statistical uncertainty is a major hurdle in performing this sort of coarse-graining. For example, if we observe 100 transitions between a pair of conformations and each of these transitions is slow, then we can be pretty sure this is really a slow transition. However, if we only observe another transition once and it happens to occur slowly, who knows? It could be that it is really a slow transition. On the other hand, it could be we just got unlucky.

Existing methods for coarse-graining our Markov models assume we have enough data to accurately describe each transition. Therefore, they often pick up these poorly characterized transitions as being important (for protein folding, we typically care most about the slow steps, so slow and important are synonymous). The new method I’ve developed (described here) explicitly takes into account how many times a transition was observed. Therefore, it can appropriately place emphasis on the transitions we observed enough times to trust while disregarding the transitions we don’t trust. To accomplish this, I draw on Bayesian statistics. I can’t do this subject justice here, but if you’re ever trying to make sense of data that you have varying degrees of faith in, I highly recommend you look into Bayesian statistics.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

September 13, 2012
Futures in Biotech video interview about FAH

This video is a year old (and we've previously posted the audio), but looking at this again, a lot is still relevant (and we didn't post the video url), so here it is in case people are curious:

http://www.youtube.com/watch?v=mhw95cBzk6U

Host: Marc Pelletier
Dr. Vijay Pande, Stanford's Director of Folding@home, details how the World's most powerful system models Alzheimer's and other human diseases.
Guest: Dr. Vijay Pande
We invite you to read, add to, and amend our show notes.
Comments and suggestions on Futures in Biotech.
Also thanks to Phil Pelletier and Will Hall for the great themes.
Thanks to Cachefly for providing the bandwidth for this netcast.
Running time: 1:17:43

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

September 24, 2012
New Gromacs, new you

Guest post from Profs Kasson and Shirts, UVA and Mr. Coffland

A new version of Gromacs (4.6) is coming, and we’re working to bring it to Folding@home. The new code contains a number of improvements (more than you’d expect for a minor version number!), and we’ll post about some of the individual features as we go. Not all of them will be available on F@h immediately, as some will require substantial development work over the next few months. But some of the basics are new free energy methods from our very own Prof. Michael Shirts, new and slightly faster inner-loop code, and some important tweaks to parallelization. Free energy calculations allow us to calculate things like how tightly drugs bind to proteins and the strength of attraction between protein components when pulled apart. And you, of course, know what faster inner-loop code and better parallelization mean!

Gromacs is an interesting piece of simulation software in that it’s heavily optimized both for single-computer performance (part of why we chose it for F@h in the first place) and for parallel scaling. A lot of codes choose to emphasize one or the other. But Gromacs tries to do both. That will have some interesting and useful implications for F@h particularly as we look at more and more cores on donor CPU’s (and things like GPU integration). That’s all for now; we’ll keep you posted on progress.

Thanks!
The 4.6 Core Team (Profs. Kasson, Shirts, and the indefatigable Mr. Coffland)

[Brasky]

i've got a work unit that says update core and it's taking up a gpu. i've deleted and re configured the gpu, which finished the unit that it was new assigned, and is now holding at the "update core" unit again. any thoughts on how to delete the work unit or do i need to reinstall?

[iancook221188]

what wu and client?

edit is this some thing to do with it? http://www.evga.com/forums/tm.aspx?m=1764583

[Brasky]

wu 5766, and probably f@H 2.7, not the newest one, i downloaded it from the f@h site about a month ago. gtx 580.

[iancook221188]

to delete a work unit if it fail and you have not change where it installs the work directory shoud be in c/User/*user name*/apps data/Roaming/FANclient/Work/ then find witch one the slot is for your gpu. you can find the core you want in the core file

[Brasky]

i'll mess with it when i get home. thanks for the assistance.
while i got you here, would these cpu's http://forums.guru3d.com/showthread.php?t=369642make the sr-x board relevant?

[iancook221188]

this mite help you getting it going watch this thread is it the same problem your having the E5 IB will probably work when a supporting bois is released but that does not change the fack that the SRX at the moment it a fail product i.e the bois, prise and a few other things + SB being lock does not help it case lets hope that IB is unlock fore prise they will put on the chips. a better broad for the money and socket platform is the Asus z9pe-d8 and some people have used supermircro boards this may help http://forums.bit-tech.net/showthread.php?t=241675

[Brasky]

no luck finding the data/work units, i'll just reinstall tomorrow. thanks for the assistance.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

October 21, 2012
Unified GPU/SMP benchmarking scheme: equal points for equal work

The current benchmarking calculations for SMP and GPU projects are performed on different machines since originally the SMP cores could not perform the calculations that the GPUs cores could and vice versa (GPUs were only for implicit solvent calculations and SMP only for explicit solvent calculations). With recent advances in both cores and completion of our testing of these capabilities to ensure agreement, we are now confident we can do the same work on both cores. Thus, we feel that it is time to unify GPU and SMP benchmarking, both for simplicity and fairness.

In order to complete the move towards this plan of "equal points for equal work," new GPU projects will be benchmarked using the existing SMP benchmarking scheme. Based on our internal tests, the end effect of this new, unified benchmarking scheme would boost the points for the GPU projects, both in terms of base points but also by bringing Quick Return Bonuses to GPU clients. In order to test the new scheme, we have started a GPU3 project (Project ID: 8057) and released it for beta testing. Once the benchmarking scheme has been tested, all the current GPU projects will be re-benchmarked to reflect the changes in the benchmarking scheme.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

October 22, 2012
Life with Playstation ending, FAH team continuing to look to push the envelope

For several years, we have worked closely with Sony to bring Folding@home to the PS3. We're excited about what we've been able to do. Since the PS3 started folding in 2007, we've done some really amazing things, with several announcements this year acknowledging advancements in Alzheimer's Disease, Cancer (and this link), Influenza, Type II Diabetes, and other new drug targets. We've come a long way in the last 5 years and we have a lot going on to continue our tradition of pushing the envelope into new technologies.

more info from fold@evga forum

Another thing that came out yesterday that was not as widely noticed. There has not been a post by PG at this time.

http://blog.us.playstation.com/2012/...-update-v4-30/

PS3 System Software Update (v4.30)
+ Posted by Eric Lempel // VP, Sony Network Entertainment

Next Tuesday, October 23rd, we will be releasing a new system software update for PlayStation 3 (version 4.30). With this update we have made several changes to how Trophies are displayed on your PlayStation 3. The Trophy Collection will now reside under PlayStation Network on the XMB. Trophies that you have earned playing PlayStation Vita games are now displayed on your PlayStation 3. You will also be able to see your Trophy level and progress towards the next level while viewing your trophy collection.



By the beginning of November 2012, we will retire the services available through the Life with PlayStation application. In conjunction with its retirement, we will stop offering the Life with PlayStation application to new users with the 4.30 update. This includes the conclusion of our participation with Stanford University’s Folding@home, a distributed computing project aimed at understanding protein folding, misfolding and studying the causes of a variety of diseases such as Parkinson’s, Alzheimer’s as well as various cancers.

We’d like to thank the more than 15 million users that have participated in the program since it started on PS3 in 2007. PS3 users have donated in total more than 100 million computation hours to the Folding@home project to date, and as a result, contributing greatly to Stanford University’s Alzheimer ’s disease research. Considering the contribution PS3 has made to the project, we decided to retire it as a result of discussions with Stanford University.
Vijay Pande, Folding@home research lead at Stanford University, had this to say about your contributions:

“The PS3 system was a game changer for Folding@home, as it opened the door for new methods and new processors, eventually also leading to the use of GPUs. We have had numerous successes in recent years. Specifically, in a paper just published in the Journal of Medicinal Chemistry, we report on tests of predictions from earlier Folding@home simulations, and how these predictions have led to a new strategy to fight Alzheimer’s disease. The next steps, now underway at Stanford, are to take this lead compound and help push it towards a viable drug. It’s too early to report on our preliminary results there, but I’m very excited that the directions set out in this paper do appear to be bearing fruit in terms of a viable drug (not just a drug candidate).”

[k1net1cs]

Why the vague wordings?
Does that mean there won't be WUs for PS3 anymore or...?
There's nearly zero correlation between the article's subject and content.

[iancook221188]

update the post did not relies the blog post had basically no info in it got word of this from evga forums look like PS3 and folding is coming to the end

[k1net1cs]

Holy-...didn't realize 'Life with Playstation' was a phrase of its own.
Both translated to the same conclusion of no more folding with PS3, but differed in who severed the relationship first.

Any reason why PG has to rely on 'Life with Playstation' for folding in PS3?

[iancook221188]

i don't know much about the PS3 or 'Life with Playstation' as i never own a PS3

[k1net1cs]

PantherX, where are you?

[PantherX]

Originally Posted by k1net1cs

PantherX, where are you?

Real life is keeping me very busy

Unfortunately, I can't add much to what has already been posted by Sony and by Dr.Vijay.

All I can hope is that there is F@H in the next version of the Play Station (This is not any inside information or any fact or anything, just my opinion)

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

The Folding@home article on Wikipedia is now a Featured Article

Here's a guest post from Jesse Victors, one of the volunteers helping with Folding@home documentation.

I am pleased to announce that the Folding@home article on Wikipedia is now a Featured Article. Following a peer review and a thorough month-long discussion, other editors agreed that it met the Featured Article criteria. This means that it's encyclopedic, well written, comprehensive, well researched, neutral, stable, and uses summary style. If you are new to the Folding@home project, or would like to learn more, I would highly recommend that you read this article. There are plenty of details on all aspects of Folding@home, but I tried to avoid technical language so it should be understandable by almost anyone. I've also summarized many of publications from FAH (see the Papers page) as well as other scientific literature, which can be helpful if you're curious about how this project works or what it has accomplished so far. The article is currently scheduled to appear on Wikipedia's Main Page as a Featured Article of the Day on November 1st, so keep an eye out for that!

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

October 30, 2012
Version 7.2.9 of the Folding@home software is now available

We are happy to announce that version 7.2.9 of the Folding@home software is now available at folding.stanford.edu. The ultimate goal of Folding@home has always been to support disease research but we've also understood that one of the best ways to do this is to make folding fun and easy. This is why we continual push to make the Folding@home software easier to install and use while still adding advanced features for power users optimizing their machines for maximum points. This software release makes strides forward on all fronts.

One of the more visually interesting and fun features is our much improved 3D viewer. It is now able to display proteins from many more folding projects, works on more graphics cards and uses less CPU time. This code is also being used as the basis for the upcoming screensaver which is currently in testing.

Those with the latest and greatest hardware will be glad to know that this version supports automatic updating of the GPU white-list. In practical terms, this means Folding@home will be able to support new graphics hardware more quickly, as it becomes available and with out requiring new software. We will publish a new GPU white-list periodically and the client will automatically update its list of supported GPUs on startup.

We are also proud to announce that we recently hired OSX guru Kevin Bernhagen. He has been working hard to bring the OSX release up to our standards. With the v7.2.9 release we are taking the v7 software for OSX out of beta for the first time. There is still much work to do but this release should offer many improvements over the v6 beta that was previously the recommend release for OSX and should integrate better with the OSX environment better than the previous beta software.

Many other improvements have been made. The folding forum thread titled FAHClient V7.2.9 (8th Open-Beta) lists the changes in more detail. While you're at it, join in the forum discussions and let us know if you run into problems, have a great idea or just what to tell us about the awesome new folding rig you've setup.

We are far from done improving Folding@home. Many new features are in the works including simpler installers, even better OSX support and easier more intuitive user interfaces. There are also some surprises on the drawing board which we are very excited about but not yet ready to announce. So stay tuned and thank you for continuing to help support disease research at Stanford and universities all over the world.

[iancook221188]

From the Official FAH Blog:
http://folding.typepad.com

November 06, 2012
Update on on-going software development in FAH

We have several on-going software development efforts and I'd like to give donors an update.

v7 client. Joe Coffland and his team have been working hard on new client releases. 7.2.9 has just been released and a new version will be undergoing beta testing soon. Moreover, we are continuing work on improving the v7 client for windows and squashing the remaining bugs. Moreover, there's additional effort in OSX due to the hiring of a programmer (Kevin Bernhagen) just for the OSX client, as well as additional work for smoother OSX and linux installs.

Gromacs core. The Gromacs core team (Prof. Michael Shirts and Prof. Peter Kasson and their labs, at the University of Virginia) are working on the new cores based on the new version of gromacs (4.6).

New OpenMM core. The OpenMM team at Stanford (Dr. Peter Eastman and Yutong Zhao) are working on speed improvements for OpenMM (the basis of the FAH GPU core) in general, but in particular optimizations for Kepler and AMD (in coordination with engineers at NVIDIA and AMD, respectively). Yutong has a new FAH GPU core working in the lab and we are doing internal testing on it. Since openMM is full open source, you can see more details, including a commit and change log, at the openMM web site (https://simtk.org/home/openmm).

New FAH viral ad campaign. We're also working on a new landing page for FAH and a new video to advertise FAH. This new web/video campaign is coordinated with new client/installer changes to make FAH easier to install and run, especially for those new to Folding@home.

We understand that donors don't get to see all of what's going behind the scenes, so we'll try to post these sorts of updates more frequently.

[Brasky]

well, i can't get the 8018 work unit to fold on the 580's, new or old drivers, stock specs. guess i'll just cpu it for a bit.