On Saturday May 30th, 2015, the Huntington’s Disease Society of America SF Celebration of Hope will Honor Prof. Pande for his work with Folding@home. Details are in poster to the right (click on it to enlarge it) and this link.
I’m happy to announce our participation in the Cancer Systems Biology Scholars (CSBS) program, which provides a unique opportunity for postdoctoral training in cancer systems biology in a dynamic, multi-disciplinary environment. A diverse group of mentors, all with independently funded research projects in cancer research, participate with expertise in many disciplines. CSBS trainees will conduct research, participate in specialized coursework and seminars, and attend a regular meeting of CSBS mentors and trainees, as part of an integrated, two-year program.
For those looking to be a postdoctoral fellow in the program, I encourage you to apply:
This would be an opportunity to work on Cancer in the Pande Lab/Folding@home or with any of the other mentors associated with the CSBS at Stanford. The application deadline is March 2, 2015. Priority will be given to applications received by March 2. Applications received after March 2 will be considered until positions are filled.
In Project 10471 we at the Chodera lab are looking at Src kinase. The Src gene was first discovered as responsible for the tumorogenicity of Rous sarcoma virus. This gene is also present in animals, and it is in fact a mutated Src gene that is injected back into the host that causes cancer, not a viral gene. The discovery that cancer was a result of mutated naturally occuring genes and not viral ones was a milestone in cancer research and Harold E. Varmus and J. Michael Bishop were awarded the Nobel Prize in Physiology or Medicine for this and related discoveries of the cellular origin of retroviral oncogenes in 1989.
Since then Src has been found to be over-expressed and/or highly activated in a variety of cancers, most notably linked to metastasis in breast, prostate, and colon cancers. The drug dasatinib of Bristol-Myers Squibb (Sprycel commercially), has been approved for treatment of CML (described more fully in our blog post on Abl kinase), but it was also recently in clinical trials for metastatic prostate cancer due to its affinity for Src kinase.
We are not only interested in Src kinase for its intrinsic value, but also to compare and contrast its behavior with Abl kinase in Project 10472. While dasatinib targets both Src and Abl kinase, only Abl and not Src is sensitive to the drug imatinib, despite the nearly identical imatinib bound poses seen in the Src and Abl crystal structures (pictured). Because these static structures are so similar, we are looking forward to using the long timescale simulations of these two kinases on Folding@home to help us understand their different small molecule binding properties.
As part of our recent assignment server upgrades we are rolling out a new psummary page (which lists all of the active Folding@home projects). This new page includes projects which are no longer visible in the old psummary system. The new psummary uses a more modern HTML but is otherwise the same.
We have aimed to make psummary backwards compatible with 3rd party tools which parse this data. However, there may be some inconsistencies depending on how these tools operate. To help eliminate such problems in the future we have exposed psummary in JSON format via the AS here:
The new psummary is here:
The previous HTML psummary will continue to be found here for a while:
Note , we plan to eventually deprecate the old psummary and therefore encourage 3rd party tool creators to update their software to use the new URL as soon as possible.
I’m excited to announce today our new initiative for Folding@home on Android Mobile phones, with a beta version being released today. In collaboration with Sony, we have brought Folding@home to Sony Mobile phones starting today with broader Android support in the coming months. The rationale for moving FAH to mobile phones is simple: there are millions of phones and they are becoming extremely powerful. Indeed, with our open source OpenMM code (http://openmm.org) optimized for mobile phones, we get performance comparable to what we were getting on desktops just a few years ago. Moreover, we have completely rewritten our server backend in order to handle the needs of mobile devices. In particular, our Streaming Backend (also known by its internal project name ‘ocore’) can seamlessly distribute work from one phone to another, so even a short amount of compute time on a phone can make an immediate contribution to our project.
With the computer power available, we plan on tackling two key challenges. First out the door is a project on breast cancer. In this project, we are investigating the nature of drug resistance mutations in key proteins (kinases) that are targets for breast cancer drugs. By studying the nature of how these mutations change these key drug targets, we will be able to both advance our basic biophysical understanding of these key proteins as well as build a tool to be used for patient specific breast cancer treatment –– by sequencing the tumor and seeing what mutations are present, our tool seeks to recommend the best drug for a specific patient. Next, we plan to follow this project with a protein folding project, related to misfolding disease (eg Alzheimer’s Disease).
Note that this is a first beta release and certain elements are not in place just yet. Nevertheless, we’re very excited about this next step forward, both that we’re moving into a new space but also that we’ve put the pieces in place such that mobile can make a significant contribution. We have other projects going on as well, so look for other announcements in 2015 for additional FAH initiatives.
Now we have over 1 millisecond of data for rhodopsin, a key signaling protein in vision. In the new year, we will be running more simulations to get better statistics on the behavior of key conformations and delving into the mechanisms of this protein’s conformational changes in response to light.
Happy New Year!
Given some known driver issues with recent NVIDIA maxwell chips and Core18 ( https://www.reddit.com/r/foldingathome/ … l_support/ ), we are temporarily restricting our core18 projects (e.g. 1047*) to use pre-maxwell GPUs. We’ll be making the changes Friday morning. Hopefully this restriction will be a temporary fix, with full maxwell support for FAH in NVIDIA drivers (fixing an OpenCL bug) in the (hopefully near) future.
You can follow this thread in the FCF:
You may have noticed a trend in the type of proteins being simulated on Folding@home recently. A number of Folding@home labs are collaborating in an attempt to understand the role of protein conformational heterogeneity (the diversity of structures a protein can readily adopt) in the binding of small molecule drugs that target kinases, proteins that are mutated in a variety of cancers. A number of targeted kinase inhibitors have already been approved by the FDA, and have been shown to significantly improve the lives of patients with breast cancer, as with HER2 inhibitors, chronic myelogenous leukemia, as with Abl inhibitors, and other cancers. We’ve put together an informational poster with the FDA approved small molecule kinase inhibitors. Almost half of these molecules target kinases running on Folding@home: Lapatinib and Afatinib target HER2 (projects 9104-9114); Imatinib, Dasatinib, Ponatinib, Nilotinib, and Bosutinib target Abl (project 10472); Gefitinib, Erlotinib, and Afatinib target EGFR (project 10473); and Dasatinib and Bosutinib also target Src kinase (project 10471). Stay tuned for more blog posts on our progress in this area.
PDF available here: kinase_inhibitor_dorm_room_poster
One major benefit of the new Folding@home streaming infrastructure (FSI) over the previous FAH “classic” infrastructure (FCI) is that FSI is streaming. So we get clients running on a trajectory 24×7, whereas FCI has timeouts which can take a while to meet, thus making long trajectories harder to calculate.
Longer trajectories are important to us because Markov State Models (MSMs) need some minimal trajectory length to be useful. The streaming approach gets us there faster and more efficiently (in wall clock time) with fewer wasted Work Units.
A quick heads up for Folding Forum users-
SiteGround, who hosts foldingforum.org will be changing the IPs of their cloud servers this Friday, December 5. The change is required in order to ensure better network maintenance and availability. The change should be invisible to most foldingforum.org users. If you get a “Not Found (404)” error message when trying to view the site, try emptying your browser’s cache or flush your computer’s DNS cache and foldingforum.org should show up.