Stanford IT managed to finish their work earlier than expected. The stats system should be back up and operating normally.
The stats server will be down between December 7th and the 9th. Points will not be accessible during this time, but will still be accruing.
We experienced some technical issues with one of our client-side servers (fah-web.stanford.edu).
And have worked hard to solve this.
Which resulted in a server transfer and new urls for:
Have changed to:
Our new feature monthly stats has new urls aswell:
Our http://fah-web.stanford.edu/ is still down and Stanford IT is working on it which means that our resources on that page are still unavailable.
Thank you for your patients.
We’re experiencing some technical issues with one of our client-side servers (fah-web.stanford.edu). Stanford IT is working hard to get things working again, but in the meantime individual and team points data might not be accessible (however all work units should receive credit). We’ll post an update as soon as things are up and running again.
Core 21 (OpenMM GPU) issues with new Windows NVIDIA drivers 375.57 (released 10/20) and 375.63 (released 10/23)
We have received a number of reports that the recent release of Windows NVIDIA drivers 375.57 (released 10/20) and 375.63 (released 10/23) is causing many core 21 (OpenMM) projects to fail. We don’t yet know the cause of this problem, but are actively investigating it.
In the meantime, we strongly encourage you to stick with or downgrade to the last known working Windows NVIDIA driver (372.70) if you would like to continue folding core 21 (OpenMM) GPU projects.
If you have already upgraded to 375.57 or 375.63 and are experiencing issues, we encourage you to report your issues to the NVIDIA Driver Team:
Thanks for bearing with us, and we hope to have a solution soon.
~ The Folding@home core 21 team.
In our regular updating of FAH systems, we’ve done a recent update of the stats website internals to help speed them up and bring them to new infrastructure that should be more reliable. Along the way, lead FAH Programmer Joseph Coffland added a suggestion from FAH Marketing Relations lead Anton Thynell to include a new sort of competition: a monthly leaderboard.
This monthly leaderboard will naturally give the top donor and top team for each month and we will collect the top leaders for each month for recognition over the year. Our intent was to give new donors a way to more directly see their contribution immediately and to in general encourage more friendly competition that helps us push forward our science even faster.
The updated page is found here:
OpenMM is our main GPU code, fully open sourced, that drives FAH. OpenMM has its roots in the original FAH GPU code, the first GPU code for molecular dynamics. Core15 represents that very long history and it’s time for us to move on and retire that Core as its code is old and outdated. Unfortunately, that means that some older GPUs (that are not supported by OpenMM) will no longer be supported by FAH.
OpenMM 7.0 has just been released and represents several key advances in speed and science. We’re working to bring this into a new FAH core shortly to continue pushing the envelope of what FAH can do. Look for that core in more extensive testing shortly.
The so-called “guardian of the genome”, p53 is a tumor suppression protein involved in regulating cell repair and apoptosis. Many cancer cells are able to proliferate because they have mutations to p53, making it the focus of intense interest for cancer researchers.
In the cell, levels of p53 are usually kept low through the action of another protein, MDM2, which binds to the transactivation domain (TAD) of p53 and recruits it for degradation. Upon binding, the p53 TAD folds into a helix and packs into a binding cleft of MDM2. Over the last ten years, there have been many efforts to develop cancer-fighting molecules that can mimic the p53 helix and competitively bind MDM2, resulting in the up-regulation of p53.
MDM2 is interesting for another reason: NMR experiments show that in the absence of p53, the disordered N-terminal region becomes partially structured and associates with the cleft. This so-called “lid region” can be seen making key interactions with MDM2 ligands in co-crystal structures, which suggest that the ability to predict likely lid conformations might be very important to rational drug design.
In a new paper in Scientific Reports, researchers from the Voelz lab have applied the power of distributed computing through Folding@home to study the conformational dynamics of the MDM2 lid region, to discover just how important modeling the lid region may be. Markov State Models (MSMs) built from simulated trajectories of the lid region show that the lid associates with the binding cleft in a two-state manner consistent with experiment, and furthermore that this motion is coupled to the opening up of the binding cleft. Since the published NMR structure of MDM2 has a closed cleft, the researchers then went on to see if known ligands could be successfully docked into the simulated MDM2 receptor structures. Remarkably, this procedure was highly successful, comparable to the “gold standard” of cross-docking ligands across a set of high-resolution co-crystal structures.
These results have important implications. For one, they suggest that large-scale simulations can help refine “bad” receptor structures for the purpose drug design. This might be particularly important for homology models of protein structures, for which computational docking often fails. The results also suggest that modeling disordered regions in proteins might be more important that previously thought.
Mukherjee, S., Pantelopulos, G. A., & Voelz, V. A. (2016). Markov models of the apo-MDM2 lid region reveal diffuse yet two-state binding dynamics and receptor poses for computational docking. Scientific Reports, 1–10. doi:10.1038/srep31631
The stats system has now returned to normal operation. Sorry for the delay and any inconvenience this outage may have caused.
A handful of Stanford-hosted FAH servers—including a stats server— will be undergoing scheduled maintenance starting today until Thursday. Assignments and points should not be affected; however, points may not be correctly reported on the website until after maintenance is completed.