[独立平台] [生命科学类] Folding@Home

vmzy

PG Member Paul Novick Thesis defense: drug repurposing successes so far
January 16, 2014 by Vijay Pande ·
Today is an exciting day, as Paul Novick (one of the Pande Group members working behind the scenes, from a FAH perspective) is giving his thesis defense today.  The title is ”Computationally Guided Re-purposing as a Drug Discovery Strategy”.  For those in the Stanford area, it will be in the Alway Building, M114 (Med School).

As a teaser and intro, here’s an intro to what he’s been working on:

Over the past several decades, the ability of the pharmaceutical industry to develop novel, impactful new therapies has diminished to the point where many formerly industry leading companies are now facing unsustainable business models. Development of a new chemical entity from initial target identification is now estimated to take 14 years with a price tag approaching $2 billion dollars. With many revenue driving therapies coming off patent within the next few years, there are serious concerns about the ability of the pharmaceutical industry to continue to finance innovation and the development of promising new drug candidates. In order to maintain solvency, heavy investments have been made in research technologies – such as genetic sequencing and analysis, high throughput screening, and combinatorial chemistry, among many others – promising to deliver faster, cheaper development timelines. Unfortunately, these approaches have yet to yield the dramatic improvements in research efficiencies that the industry so desperately needs.
Paul will talk about the solutions we have developed to tackle these issues, by combining computation and drug repurposing.  This has yielded novel treatments for Chagas Disease and Dengue fever.
大意：
PG小组成员Paul Novick今天论文答辩，论文题目是‘药物研发领域的新武器——通过计算发现已有药物的新用途’。
论文概要：在过去几十年里，由于商业模式的不可持续发展，传统制药产业的新药物研发越发止步不前。开发新药的药物筛选工作大概要耗费14年时间、20亿美金。由于老药品的专利保护期限将至，而新药物又青黄不接，这时老企业的财务就会面临巨大问题，甚至破产。为此，制药企业会尽可能的采用新技术（例如：基因测序、高速筛选、组合化学……）加快研发。但不幸的是至今这些新技术都没有产生预期效果。
Paul将就此问题提出一个利用计算和药物重筛的新解决方案。这种方法已经在查加斯氏病和登革热方面产生了新的疗法。

金鹏

Update on PPD calc in latest v7 client

January 17, 2014 by Vijay Pande ·

We’ve gotten donor feedback regarding issues with the Points per day (PPD) calculation in the latest client v7.4.0 beta.  Here’s an update.  After a code review, we see that v7.3.11 used the timeout (aka preferred deadline) not the deadline (aka final deadline) in the bonus calculation.  This is now fixed in the source and will be rolled out in an update.

Filed Under: Uncategorized ·
大意：
用户反应最新版的PPD计算有问题。经过代码审查后发现从7.3.11版起就出了问题。我们会尽快发布修正版。

vmzy

CPU counts, FLOPs, and corporate partnerships
January 20, 2014 by Vijay Pande ·
One question that has come up recently is that the count of the number of CPUs involved in FAH has gone down quite a bit in the last 3 to 6 months.  There are several factors going on here.

We frequently negotiate periods of time to run on the machines in corporations, as this can bring a lot of power to FAH.  In most cases, the donations we get from large corporations are for pre-set lengths of time. These companies have some campaign or some period of availability. We’re constantly negotiating with companies for such partnerships and so the fluctuations in the number of computers may be quite great, especially as the number of single-core clients changes rapidly.

Also, in recent partnerships,  GPUs and large-core CPUs were emphasized over lots of single core CPUs and so the count of the number of machines will likely go down quite a bit but the FLOPs will remain quite high (today we’re still about 15 Petaflops, which makes FAH a very, very powerful supercomputer, especially when you consider that other traditional supercomputers would underperform their reported FLOP count if they used FAH’s approach at calculating FLOPs).  In the end, a high FLOP count has a big impact on our work.

With that said, it is very important for me to emphasize that we value all contributions.  Indeed,  we have in the past (and will continue to show in the future) shown the power of how many computers, even single core PCs, can band together to do amazing things.  Towards those ends, we have in particular been working on a new server backend software which can more efficiently utilize the results from many single-core CPU machines.

As I see it, the future of FAH will have to be heterogeneous and may even in the future incorporate mobile devices.  In the coming weeks, we hope to roll out our plans there more publicly, with some new initiatives on the CPU side which I think could greatly increase the power of FAH.
大意：
近期的问题是，在过去的3-6月里，活跃cpu数大幅减少。
目前我们在和一些公司协商合作（译注：主要是不作恶的google）。当他们服务器比较闲的时候跑单核版fah。所以今后单核版客户端统计数量，会经常大幅波动。
GPU和BA客户端增幅明显，所以即使机器统计数量大幅减少，但是FLOPs（计算量）并没有减少（fah目前有15P的计算量，更不要说我们的计算算法比超算跑分程序更复杂）。
单核任务同样重要，为此我们将开发一套全新的后台，以便能更有效的利用单核任务的结果。
将来fah的客户端将更加多样化，甚至出现移动版客户端。后面几周，我们将公布更加详细的计划，我们相信新的措施会大幅刺激cpu客户端的增长（译注：要加cpu的奖励系数了？）。

vmzy

Watch FAH/PG code development in action
January 21, 2014 by Vijay Pande ·
Donors have often asked how they can see more of what’s going on behind the scenes.  One way to do that is to check out the various code development projects we have going on at github.  You can see some of the key tools being developed at https://github.com/SimTk, including OpenMM (the software behind Core17) and MSMBuilder (the software behind how FAH analyzes WUs).
大意：
FAH开源库，感兴趣的可以去看下源代码，包含OpenMM（Core17）和MSMBuilder （结果分析工具）

金鹏

Improvements to the AS for older single-core, clients
January 22, 2014 by Vijay Pande ·

We’ve made some changes to the Assignment Server to improve the ability for older, single core (i.e. not SMP) clients (pre-v7) to get WUs.  The v7 client merged the SMP and the single core clients and it (and the v6 SMP client) reports information slightly differently enough that it could lead to issues with older single-core, v6 clients getting assignments.

This is updated AS is running on the main AS and looks to be behaving well.  We will migrate it to the other AS’s shortly.

大意：改了下AS服务器代码，对老版本客户端（尤其是单核版）提供了更好的兼容性。暂时只在主AS服务器上做测试。测试完成后会部署到所有AS服务器上。

New FAH tshirts
January 22, 2014 by Vijay Pande ·

Several donors have asked me how to get FAH tshirts.  We’ve set up a url at teespring for those who’d like to get a shirt.  The profits go to Stanford to support FAH development.  Please go to http://teespring.com/folding if you’d like to get one.

大意：

很多志愿者在问FAH纪念体恤的事情。为此我们专门做了个页面（卖纪念体恤），所得利润将全部用于FAH开发。
译注：哪位先吃这只大螃蟹？

vmzy

NVIDIA GPU Technology Conference (GTC)
January 23, 2014 by Vijay Pande ·
I’ll be speaking at the NVIDIA GTC on our recent work in cancer.  Specifically, it’s talk S4133, entitled “OpenMM Molecular Dynamics on Kinases: Key Cancer Drug Targets Revealed with New Methods and GPU Clusters” and it is scheduled for 50 minutes on Tuesday, 3/25/2014 at 2:30:00 PM in Room LL21E.
大意：
Vijay Pande将于3/25/2014 下午 2:30在 LL21E教室出席NVIDIA GPU技术大会。做50分钟有关利用gpu进行癌症研究的演讲。

金鹏

Papers page updated
January 24, 2014 by Vijay Pande ·

We’ve added a few papers to the Papers page.  The most important application result is our work on GPCR intermediates as new possible drug targets.  We also have several new methodological advances which are proving important for our work going on right now.

Coming up (hopefully) soon will be a paper on new drug targets involving kinases, key protein targets involved in fighting cancer.

大意：论文页面更新，加了几篇论文。其中最重要的是GPCR 媒介的研究。同时还有几篇方法论方面的新研究。
接下来的重头戏就是抗癌方面——激酶的研究论文了。

金鹏

Kinase paper accepted in Nature Communiations
January 28, 2014 by Vijay Pande ·

Our recent work on simulating kinases on Folding@home and the simulation’s use in identifying potential new cancer drug targets has been just accepted for publication in Nature Communications this morning.  I’ll post more in the coming weeks with more details after the paper is past Nature’s embargo period.

大意：关于利用激酶进行抗癌药物研究的论文已经被自然杂志接受，待保密期过后我会公开部分细节。

vmzy

OpenMM webinar
February 10, 2014 by Vijay Pande ·
I recently gave a webinar on OpenMM, the heart of our Core17 for GPUs (and also now more recently, high performance computing on multi-core CPUs as well).  Here’s a link if you’re curious to learn more:
http://on-demand.gputechconf.com ... -openmm-webinar.mp4
大意：
最近召开了OpenMM（GPU内核core17的核心技术，也是多核GPU的核心技术）的网络研讨会。

vmzy

Update to stats system accounting of ATI GPUs
February 17, 2014 by Vijay Pande ·
We’ve been suspicious that the stats system has been undercounting ATI/AMD GPUs for some time now and we have found the issue.  We’ve rolled out an update to the stats code and so we expect to see more ATI GPUs showing up in osstats.大意：
我们发现貌似少统计ATI/AMD GPUs数量了，我们更新了统计脚本。A卡数量应该会大涨一下。

vmzy

Registration open for a free webinar: The Next Steps for Folding@home
February 18, 2014 by Vijay Pande ·
I’ll be presenting a webinar on Folding@home open to the public on Tuesday, May 27, 2014 9:00 AM – 10:00 AM PDT.  You can register on this link: https://www2.gotomeeting.com/register/688201986.  The goals are to talk about what we’ve been able to do so far and where we’re going.

Summary.  Folding@home is a large-scale volunteer distributed computing project, started in October 1, 2000. For over a decade, new types of hardware (such as GPUs, multi-core CPUs, and PS3) and algorithms have been pioneered in order to make significant advances in our ability to simulate diseases at the molecular scale. Join Professor Vijay Pande from Stanford University for a brief introduction to the goals of Folding@home, followed by the successes so far. Prof. Pande will end with a discussion of what’s being done today, as well as the plans for greatly enhancing what Folding@home can do through new initiatives currently under way.

Please note that this webinar starts at 9:00 AM Pacific, 12:00 PM Eastern, and 5:00 PM BST.
大意：
计划于5月27日由Vijay Pande主持召开网络研讨会，讨论FAH的前世今生以及将来发展，现开放注册，有兴趣的（鸟语听力好的）赶紧去注册吧。

金鹏

FAH at Biophysical Society
February 24, 2014 by Greg Bowman ·

The Biophysical Society, an international group that brings together researchers taking a physical perspective on biology, just had its annual meeting in San Francisco.  A number of us involved with Folding@home gave talks and/or posters and there was tremendous interest in what we’re doing.  So, thanks to all of you for your help in facilitating great science!

大意：生物物理学组织在三藩市开年会，我们的人也参加了。很多人对我们的项目感兴趣。


Adding a completely new way to fold, directly in the browser
February 24, 2014 by Vijay Pande ·

Through a collaboration with Google, the Huang lab at  UST Hong Kong, and the Pande Lab at Stanford University, we’ve been working on a new way to run Folding@home –– through the browser.  The primary goal here is to make folding much easier to run, especially for non-expert computer users.

Open beta.  We are happy to announce that we now ready to release a first open beta test of the web client.  It uses Google’s Native Client (aka NaCl) technology, allowing one to run Folding@home in a browser.

If you’re curious to check it out, you can go to the FAH Chrome Store link.  Note that this only runs in Chrome (minimum version 31).  For support questions, we have created a new subforum at foldingforum.org.

Requirements.  In order to use the Folding App, you need to cover these three basic requirements:
1) Use the Chrome Browser (Details) in Windows, Linux, or MacOS-X
2) Install the Folding App from the Chrome Web Store (Details)
3) Launch the Folding App and you are now folding!

Please note that there are some additional options which you can use to enhance your Folding experience:
1) You may configure the Folding App with a username (Details), Team number (Details) and a passkey (Details) though none of these are required.  Please note that passkey is needed if you want to earn additional points for successfully finishing the Work Unit (WU) quickly.
2) If you don’t want to install the Folding App, you can always use the direct link in any Chrome Browser installed on Windows, Linux and OSX (Details).

Open source.  This is the first F@H Client that is fully open sourced. The F@H Native Client (NaCl) uses a new Assignment Server (AS) and a new version of the Work Server (WS) which exposes a JSON interface with additional security for third party developers. The folding is done on a Gromacs (version 4.6.5) based FahCore which is closed-source for security reasons. Third party developers are encouraged to participate in the development (Details) and users can also keep track of open issues (Details). Developers can view the log file generated from NaCl by choosing the console view from the DevTools Window.

Next steps.  Finally, as many will probably notice, this opens the door to naturally moving Folding@home from the browser on a computer to a browser on a phone or tablet.  We are actively investigating those possibilities.

Some links to additional related material:

Folding App Source Code: Details
Folding App FAQs: Details
Third Party Forum: Details
Folding@Home Homepage: Details
Chrome DevTools: Details

大意：
FAH网页版客户端正式公测
FAH与谷歌合作利用Native Client技术开发了纯网页版客户端（只能在chrome浏览器上跑，最低要求31版）。可以在Chrome Web Store里下载安装（也可以通过链接手动运行）。安装后别忘了填用户名、团队以及passkey。
该版客户端是开源的，有兴趣的可以去看下。AS和WS服务器都是专设的（支持JSON格式接口）。计算内核使用Gromacs 4.6.5修改版（由于安全原因，该内核不开源）
后续：将来可能支持手机及平板上的chrome浏览器，我们现在还在做技术调研。

金鹏

New FAH research in Cancer published in Nature Communications
March 5, 2014 by Vijay Pande ·

Our paper “Activation pathway of Src kinase reveals intermediate states as targets for drug design” in Nature Communications has just come out.  As with Nature journals, it’s unfortunately behind a pay wall, but per NIH rules, it will become open access in a year.  The key results in this paper is the use of FAH simulations to understand a key protein target in cancer (src kinase), especially to find new ways to target it for novel drug design.

A more technical summary is given in our abstract:

Unregulated activation of Src kinases leads to aberrant signaling, uncontrolled growth and differentiation of cancerous cells. Reaching a complete mechanistic understanding of large-scale conformational transformations underlying the activation of kinases could greatly help in the development of therapeutic drugs for the treatment of these pathologies. In principle, the nature of conformational transition could be modeled in silico via atomistic molecular dynamics simulations, although this is very challenging because of the long activation timescales. Here we employ a computational paradigm that couples transition pathway techniques and Markov state model-based massively distributed simulations for mapping the conformational landscape of c-src tyrosine kinase. The computations provide the thermodynamics and kinetics of kinase activation for the first time, and help identify key structural intermediates. Furthermore, the presence of a novel allosteric site in an intermediate state of c-src that could be potentially used for drug design is predicted.

大意：
有关癌症（激酶）的论文已经发表在自然杂志上了，不过由于NIH（美国国立卫生研究院）的要求，目前该文章收费，1年后才能免费访问。
技术摘要：
激酶的异常活跃可以导致机体信号紊乱及癌细胞增生。为了彻底了解激酶的大规模构型变化，我们借助了分子动态模拟技术进行模拟。计算结果揭示了全新的变构中间态，今后有可能成为新药物研发的突破点。

vmzy

Making dramatic improvements to the models used to study proteins
March 6, 2014 by Vijay Pande ·
In our simulations, we use models (aka “force fields”) of how a protein’s atoms interact physically.  Recently, we’ve made an important advance in how to make these models, which will, in time, have a huge positive impact on Folding@home’s ability to make even more accurate predictions.

You can see a story on it in BCR and the full paper in the journal’s site.
大意：
蛋白质研究模型取得重大突破。
在我们的模拟中，我们使用模型（也叫力场）来研究蛋白质分子间的相互物理作用。最近我们在这个领域取得了重大进展。
详见杂志链接。

vmzy

Donate Bitcoins to Folding@homeMarch 13, 2014 by mpiercy

We’re grateful for all of the donations we get. Donors have often asked us for other ways to donate and we wanted to give a heads up on a new way to do so. You can now help support Folding@home by donating Bitcoins. Click on

in the “Help us reach 1,000,000!” tab. Enter any bitcoin amount (whole or fraction) you want into the window. You can also help support our research by donating using your credit card.

大意：
FAH现在接受比特币捐赠了。