Gamers, get your folding on
May 9, 2008
Technology Review was the first place I saw it, then someone put it up on Friendfeed and now Andrew Perry has a great post on Foldit. Foldit comes out of the lab of a bbgm favorite, David Baker, right here at the University of Washington.
Foldit combines gaming with protein structure prediction. It’s an interesting approach to spreading scientific problems. Folding@home built upon the success of Seti@home and the geek cred of running on gaming consoles and has built quite a following. Will Foldit, which presents a simple, fun interface to get people interested in protein structure (and the existence of Folding@home makes this somewhat familiar to geeks everywhere) be an example of how we can leverage crowdsourcing? Andrew makes some interesting points (which I agree with) on weighting crowdsourcing, although that’s always a hard thing to do, but I’d like to see karma, etc come into play here.
It’s good to see protein structure getting some attention and continuing to be creative. It’s always been my favorite scientific subject. The field lends itself to “pretty pictures”, so getting non-experts involved is a possibility.
The site and server have had connectivity issues since I’ve been trying, so perhaps they need help with web resources, cause lots seem to be interested.
Here is a list of people supporting the project: UW Animation Research Labs, UW Baker Lab, DARPA, Microsoft, and Adobe. Nice list.
Image via Wikipedia
Technorati Tags: David Baker, Foldit, Protein Folding, Protein Structure Prediction, Gaming, Crowdsourcing
HPC and structure-based drug design
May 5, 2008
Here is the abstract of a paper in Hypertension entitled Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents.
Angiotensin-converting enzyme 2 (ACE2) is a key renin-angiotensin system enzyme involved in balancing the adverse effects of angiotensin II on the cardiovascular system, and its overexpression by gene transfer is beneficial in cardiovascular disease. Therefore, our objectives were 2-fold: to identify compounds that enhance ACE2 activity using a novel conformation-based rational drug discovery strategy and to evaluate whether such compounds reverse hypertension-induced pathophysiologies. We used a unique virtual screening approach. In vitro assays revealed 2 compounds (a xanthenone and resorcinolnaphthalein) that enhanced ACE2 activity in a dose-dependent manner. Acute in vivo administration of the xanthenone resulted in a dose-dependent transient and robust decrease in blood pressure (at 10 mg/kg, spontaneously hypertensive rats decreased 71+/-9 mm Hg and Wistar-Kyoto rats decreased 21+/-8 mm Hg; P<0.05). Chronic infusion of the xanthenone (120 microg/day) resulted in a modest decrease in the spontaneously hypertensive rat blood pressure (17 mm Hg; 2-way ANOVA; P<0.05), whereas it had no effect in Wistar-Kyoto rats. Strikingly, the decrease in blood pressure was also associated with improvements in cardiac function and reversal of myocardial, perivascular, and renal fibrosis in the spontaneously hypertensive rats. We conclude that structure-based screening can help identify compounds that activate ACE2, decrease blood pressure, and reverse tissue remodeling. Administration of ACE2 activators may be a valid strategy for antihypertensive therapy.
Here’s the HPCwire story, which really doesn’t tell me much other than really high throughput docking, but they use words like
That in itself is a significant accomplishment because no one has ever specifically identified a compound that enhances the activity of an enzyme using a rational structure-based approach
Anyone have a subscription to Hypertension? I am really curious cause nothing I read screams “unique” to me. Of course, I can just wait till tomorrow and try and get to the paper from work.
Update: Got the paper, and still don’t get the fuss. It’s an elegant virtual screening strategy, but I wouldn’t say it’s revolutionary. I was hoping to see something more advanced, e.g. protein flexibility, better energy functions, etc.
Image via Wikipedia
Technorati Tags: Virtual Screening, Structure-based Drug Design, Hypertension, High Performance Computing
Bio-IT World day 2 - iPhones, Virtualization, EC2 and the Semantic Web
April 30, 2008
A quick report on Day 2 of Bio-IT World.
The day started with a keynote by Josh Boger, founder and CEO of Vertex. His talk spanned several real world examples and some food for thought. Highlights
- Vertex has made active use of a MedChem ELN, which has been extended to their entire MedChem community, including external partners. In his own words the goal was “enabling the virtual research organization”
- Metric of success was user adoption and there were some good analytics supporting uptake
- He spoke at length about the HCV program, where they have used extensive predictive modeling and simulation
- Clinical data has backed up their predictive modeling (they’re in Phase III now)
- They have avoided some experiments (carried out by competitors in one case) that their models suggested they avoid
- He ended by talking a lot about communication and how technology can impact the healthcare system. Much of this section of his talk was around the iPhone. For example how the iPhone can be used to track RFID tagged pill bottles, patient exercise regimens, carry patient records, monitor weight, etc. They’re actually implementing some of these ideas
There were many other talks to attend, and I won’t bore you with some of the details, but I will talk about one talk, a talk by Chris Dagdigian of The BioTeam, a small boutique consulting shop, which readers of this blog will know via mentions of Michael Cariaso. Chris spent a lot his talk discussing the economics of storage and the kinds of storage, etc available these days and trends in storage and computing. Perhaps it shows how much of a geek I am, but this was a dream talk, one full of hardware specs, pictures of data centers, etc. It is clear that virtualization is big; Chris’ preference being Xen. There was a cool slide on meta-virtualization (a virtual machine inside a virtual machine inside a virtual machine). Two thoughts really resonated with me; first was his distaste for classical Grid Computing, which I have long considered impractical for most companies. The second was his strong support for Amazon Web Services, especially EC2. Apparently, every single BioTeam consultant has independently deployed an EC2 solution, i.e. they’ve all come to the same conclusion. Can’t wait to see this talk next year to find out where they’ve gone with AWS. One thing he said which also resonated was to talk about the death of the small cluster. Today and in the future, we will either have multicore (8-16 cores) on our desktops or dial up cloud resources. His slides will be available somewhere. Can’t wait to get my hands on them. This was a GREAT talk.
One of the highlights for me was attending the W3C Semantic Web HCLSIG lunch. I got to meet people I know (Eric Neumann), people I have interacted with online (Vipul Kashyap) and followed (John Wilbanks from Science Commons). And I got to say hello to Sir Tim Berners-Lee, who needs no introduction.
Another highlight for me. I got to finally meet Joe Landman, whose JackRabbit got a good plug in the BioTeam talk as well. It was great to meet Joe with whom I’ve been having a conversation via our respective blogs for quite a while now.
Met several former colleagues and customers as well. Bio-IT World has definitely been one of the better conferences I have had a chance to attend in terms of interest and people.
Image via Wikipedia
Technorati Tags: Bio-IT World, W3C, BioTeam, BioIT
Rethinking software access
April 26, 2008
So today, I tried to download MODELLER which is free for academics and $$$ for commercial via Accelrys (Full Disclosure: While i did not directly manage MODELER at Accelrys, I had indirect responsibilities). I completely understand that part. The problem is that the MODELLER license does not seem to address what I want to do: hobby science. So I had to wait for my request to be approved, which it didn’t.
There’s two thoughts that arise from this exercise, or maybe three. First, it’s clear that when the MODELLER license was written, personal research use was not considered. It harks back to the assumption that “real science” was either done in industry or at companies. Well folks, it might have been true some years ago, but it is an assumption that is a bit of a problem. I completely understand that they are trying to avoid the system from being gamed, but in my mind the old model (free for academic, $$$ for commercial via another entity) does not work as classically constructed in this case, for multiple reasons. The whole licensing model does not work for bursty science either, especially when one or more non-academics is installed (this is a question that I took a hard look at once for MD programs).
Which leads me to thought #2. I come from an era when modeling software was local, either on a workstation or on a cluster somewhere. That’s how I always ran CHARMM, MODELLER, WHATIF, various threading packages, MOPAC, GAUSSIAN, various other QM packages. That is how most people run those codes today. Then think about a project that you might want to do, a bursty project spanning geeks across countries and continents. Yeah, modeling doesn’t live well on the programmable web. There are servers out there, especially for structure prediction, sequence alignment, etc, but they seem to belong to a different era of the web. We need to start thinking about the source hosted model, at least for academic code. Source code licenses that target developers and power users that like tinkering with the code, but that’s also better done by hosting all academic code at sourceforge, google code or github, so that collective intelligence comes into play, rather than people developing their own forks which no one else gets to see. Second, applications should be available on the web, ideally with APIs that make it possible to mash up solutions. Now, automating these tasks is not always trivial, neither is setup. All of us with hundreds of utility scripts know that, but lets think about the web when we develop code. Not just providing a web server, but how that server can be used as a powerful resource, not just a result submission and retrieval backend. I’d love to be able to get access to a NAMD server, run a series of utility tasks and then launch a compute job, where I could dial up a set of servers, etc. It’s also possible to attach utility based licensing and pricing to such a service.
What I am arguing for is new ways to think about how we make software available, and how it is used. This can’t be done at the individual group level, but there is an opportunity here for universities and funding agencies to figure out how they can help facilitate this, and even companies that might want to commercialize some of these packages.
Comments on this? What would you like to see? How might you access such tools? Would you want mashup APIs?
Technorati Tags: molecular modeling, web services
What if?
March 28, 2008
Source: WikipediaWhat if the result of every docking result was published online, with associated metadata link to protocol, scoring function/docking function, etc)? What if we could search across this entire space to try and come up with some conclusions? What if every docking result was an addressable resource?
Just the kinds of questions we need to ask ourselves if we ever want to understand how to bring web-scale to our science.
Technorati Tags: Docking, Web-scale computing, Collective Intelligence
