Folding@home

Visit from Jim Clark and John Hennessy (President of Stanford University)

Jim Clark has been a major donor to Stanford and his great contributions has had a huge impact on my group's work in general and on Folding@home in particular.  Jim Clark was a professor of CS at Stanford, but subsequently was involved in many successful major Silicon Valley companies (see his wikipedia page for all the details).  He also donated over $100M to Stanford to build the Clark Center, a University-wide center for interdisciplinary biology.  

Today, Dr. Clark along with John Hennessy (the President of Stanford University) visited our offices to hear about our recent work.  They both were heavily involved in computer architecture in the past, so they were interested to hear about our work with GPUs and the success we are seeing there (in particular, the significant speed increases).  Also, they are both interested in neuroscience and so I was excited to tell them about our recent Alzheimer's work.

Anyway, I was excited to give them both an update and some idea of where we're going, and it was great fun for me to tell them all about how much we've done.

Stanford Winter Holiday Schedule

Stanford will be closed for the next two weeks for the Winter Holidays (ending January 5, 2009).  FAH will still be up (FAH is always up), but we will be on a reduced staff.  FAH team members have broken up their vacations so that there will always be someone around, but the main issue is that responses to problems will likely be slower than normal.  However, we have been working to add lots of jobs, clear out lots of HD space on servers, get all the servers up, such that we should hopefully be in good shape even if there are some problems. 

We'd like to wish all the FAH donors a happy holiday and thank all of you for all your great help with our project.

New FAH results on possible new Alzheimer's drug presented

This is very preliminary news, but something I'm very, very excited about, so I'll give some advance news.  On Tuesday, we presented our results regarding new possible drugs (small molecule leads) to fight Alzheimer's Disease at a recent meeting at Stanford.  This meeting was part of the NIH Roadmap Nanomedicine center (http://proteinfoldingcenter.org/) retreat and was supported by NIH grants to Folding@home.

It's very early (so we are not publicly talking about the details until this has passed peer review), but we are very excited that it looks like we may have multiple small molecules which appear to inhibit toxicity of Abeta, the protein which is the toxic element in Alzheimer's Disease.

This is exciting in many ways.  It's been a long road for FAH to get to this point, but we are starting to see the possibility of seeing these results published easily before our 10th birthday (October 2010).  Considering all the technology development that had to be done in the first five years, these results have come very quickly (in the last 3 years), which is exciting.  In particular, we are now looking to apply these methods to other protein misfolding diseases (we have pilot projects for Huntington's Disease underway).

Finally, I should stress that while we're very excited about this, it's still early and a lot can go wrong between where we are and having a drug that doctors can prescribe.  Over the holidays, we will be double checking the experimental data, crossing t's and dotting i's to make sure there is nothing missed before we think about submitting this for peer reviewed publication.  Also, there is still a long way from an interesting possible drug (where we are now) to something which has passed FDA clinical trials (where we'd love to be), and a lot can go wrong in clinical trials in particular.  

Thus, this is an important milestone for FAH and we are very grateful to all who have contributed.  Happy holidays to all!

Planned maintenance for Stanford network over the next 2 weeks

During the next two weeks (December 20 - January 4), the Backbone Networking group plans to schedule a backbone maintenance window every morning from 4-8am pacific time to implement improvements in the network, as they did last year. In most cases, the changes should not affect the connectivity of the networks used by Folding@home. In cases where they might, any interruption in service should be under 5 minutes.

Strongly suggested update client update: new ATI GPU client 6.23

We have made several bug fixes and speed improvements wrapped into a new ATI GPU client (version 6.23).  We strongly suggest that everyone upgrade.  While current (and new cores, especially ATI GPU core version 1.22) should work with other clients, we are seeing some possible issues which the new client fixes.  

As always, we suggest that one backup their machine before upgrading software, especially in case you would like to go back to the previous version.  You can download the new client at

http://folding.stanford.edu/English/DownloadATI

and as always, please post comments in the forum (http://foldingforum.org).

PS For those with NVIDIA GPUs, you could also consider upgrading to client version 6.23 (from http://folding.stanford.edu/English/DownloadWinOther ) as it also fixes some issues.  However, this is less of a critical at the moment for NVIDIA than ATI.

Update of the EULA

We have added one word to the End User License Agreement (EULA), but it is an important word.  The EULA can be found at

http://folding.stanford.edu/English/License

We added the word "written" to this sentence:

"You may use this software on a computer system only if you own the system or have the written permission of the owner."

We felt that this was an important addition in order to avoid any confusion.  There have been a few situations where donors felt that they had permission, but the owners of the computers did not.  Having written permission is the best way to make sure that there is no doubt.  It also gives protection to the donor in that he/she would then have proof of permission, avoiding problems involving oral agreements.

New paper #60: PS3 paper

We have another paper that came out recently (paper #60 at http://folding.stanford.edu/English/Papers).  This one describes the PS3 client in FAH:

Accelerating Molecular Dynamic Simulation on the Cell processor and PlayStation 3 
by Edgar Luttmann, Daniel L. Ensign, Vishal Vaidyanathan, Mike Houston, Noam Rimon, Jeppe Øland, Guha Jayachandran, Mark Friedrichs, Vijay S. Pande. 

'In this paper, we detail how we were able to get great speed increases for Folding@home (and actually certain molecular dynamics calculations in general) on the PS3. This is our first paper using the PS3, laying out the "how does it work," with a follow up paper in the works describing the results obtained in FAH from PS3 clients. 

It is also worth noting that this paper is a collaboration between FAH team members (Luttmann, Ensign, Vaidyanathan, Houston [now at AMD], Jayachandran, Friedrichs, and Pande) with developers at Sony (Rimon and Øland and their coworkers). 

Here's the more technical abstract as well:

Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory access versus computation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors.

New paper #59: Ribosome gate

We have another paper (paper #59 at http://folding.stanford.edu/English/Papers)

Side-chain recognition and gating in the ribosome exit tunnel by Paula M. Petrone, Christopher D. Snow, Del Lucent, and Vijay S. Pande.  Proceedings of the National Academy of Sciences, USA 2008

which recently was published, representing a major step for FAH. 

This one deals with the ribosome. The ribosome is a fascinating molecular machine, responsible for the synthesis of proteins. For this reason it is of fundamental importance to protein folding (as the last step in the central dogma of biology) as well as to human health (since the ribosome is the target of a very large fraction of antibiotics). One of the questions revolving around ribosome function is why is there a large tunnel inside the ribosome, through which proteins exit after being synthesized. In this paper, we used "bigWU" classic clients (clients which allow larger systems to run) since the ribosome is so huge that it would not run on regular classic clients.

 The primary goal of this paper was to analyze the surface of the ribosome tunnel. Understanding the nature of this surface would be useful for both understanding the fundamental nature of protein synthesis as well as how key antibiotics interact with the ribosome. An interesting related discovery was the identification of a potential "ribosome gate" which can open and close selectively, based on what is interacting with the gate. This suggests novel hypotheses for several aspects of ribosome function as well as interesting new directions for work on studying the ribosome and for new routes for antibiotics.

Folding@home Alzheimer's Simulation work published

I am very happy to announce that a first key work (paper #58 at http://folding.stanford.edu/English/Papers) from the Folding@home project on Alzheimer's Disease (AD) was just published

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 

url:  http://link.aip.org/link/?JCP/129/214707

Abeta misfolding and aggregation is believed to be the cause of Alzheimer's Disease. Simulations, like Folding@home, are a natural way to understand this process. However, there are several key challenges for simulating the key step -- oligomerization. This work represents a new way to simulate Abeta oligomerization, with a key advance of being able to simulate experimentally relevant timescales and concentrations, using a novel method. We use this new method and the power provided by Folding@home donors to simulate oligomerization in all-atom detail. This has lead to specific predictions about the process, which we are now testing experimentally. 

In many ways, this paper is the "tip of the iceberg" for the Folding@home activities in AD, with a lot more interesting results to come, especially in terms of experimental tests of our predictions and interesting new possibilities for new drugs and AD therapeutics.  So, while we're excited that this result is now past peer review, we're even more excited for what's coming down the pipeline, waiting peer review.  We'll keep you posted as more results become public, hopefully with some even bigger announcements in 2009.

UPDATE:

It was asked which clients participated.  This work started several years ago and took some time to analyze and then publish.  So, it ran exclusively on classic clients.  For the follow up simulations, we are using a mixture of GPU, SMP, and classic clients.  Due to the large number of classic clients, they allow us to calculations not possible on the other platforms.  However, the raw speed (but smaller number) of the GPU and SMP clients allow us to get a good rough idea quickly, refining later with classic clients.

Long term vision for FAH: Science, clients, etc

It's been a while since I've posted on this topic, so I thought it would be a good time to talk about the long term vision for FAH.  In the first few years, we have done a lot to build up methodology (novel distributed computing algorithms, tests of methods), especially in the last years working to bring GPU's, PS3's, and tightly coupled SMP calculations to a distributed computing platform.  While all of this has been going on, there has been a lot of work which would have a direct impact to disease and human health, and donors should see more results (i.e. papers) coming out in this direction soon.  In particular, results on Alzheimer's Disease, Huntington's Disease, and some other surprises in the works (sorry, some details are best left until peer review is done).

In terms of a long term vision for the FAH software, our short term goals is to shore up the SMP client.  Just as there was a big improvement from the GPU1 -> GPU2 client, we have been working steadily on an SMP2 client -- a version which is much easier to use, requires less donor effort, and scales much better.  This really is a combination of a modified client and (especially) new cores.  This effort has been going on for about a year and it's far enough along that I'm starting to talk about it publicly.

In the previous post, I also mentioned about some of our work behind the scenes in revamping the backened of FAH, i.e. a whole new set of server codes.  We have code for the workserver and collection servers, but in time we expect the full backend to be cleanly rewritten from scratch.

Longer term, with a more solid GPU2 and SMP2 clients done, we can then move on to other areas.  Our goal is to be bleeding edge in the nature of our science, but get back to the simplicity and stability found in the classic client.  We still have a ways to go, but I am excited that projects that were started some time ago are now looking like they will see the light of day.