I'm at the annual rosetta developers conference which started yesterday and goes through saturday. There are 90 developers from all over the world attending, and there has been a very exciting mix of new algorithmic developments and exciting applications to important biological and medical problems.

In a few weeks I will be describing our work on vaccine design at the upcoming HIV vaccine meeting in Seattle: http://www.hivvaccineenterprise.org/conference/program.html, maybe some of you will be there!

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The first game prototype is now online! we've put almost all of our efforts into a much more sophisticated version in which the game player collaborates with his/her computer and other players to solve difficult problems, but as an intro Ian Davis has put together a simple Java version that you can play without downloading anything on to your computer. we hope to build this into a fun way to explain the science we are doing on rosetta@home and as a warm up to the multiplayer human + computer version. Here is Ian's recent post, which you can also find on a thread he just started elsewhere on these pages:

Hi R@H community,

I've been working with several others in the lab on an "interactive Rosetta" project. The vision is that one day, you'll be able to interact with Rosetta as it runs, both (1) to help it produce better results and (2) to learn about what it's doing.

We're not there yet, but we have an early prototype for #2, the educational side. This is a simple "game" you can play in your web browser (using Java) to find the missing side chain for a designed protein that might be used to fight cancer. In this case, there's a small number of choices and the right answer should be obvious. However, it illustrates one of the basic steps that Rosetta performs thousands of times every time it designs a protein.

More "levels" for the game will be coming in the future. Also we're already planning to change the interface on the Java applet and to add a "score board" so you can compete against others, but if you try it out and have other comments or ideas to share, please post them here.

Here's the link: the Rotamer Game

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Here's the link: the Rotamer Game

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Rosetta Moderator: Mod.Sense

The results of the last few days of computations of Rosetta@home on your computers have been pretty amazing! In collaboration with a group at the NIH, we experimented with adding a very small amount of information about protein structures from nuclear magnetic resonance experiments to the rosetta structure prediction process. this information is fairly easily obtainable, and doesn't seem like it would have much effect, but the results show quite contrary--the models produced are extremely accurate! this has the potential to revolutionize how scientists determine protein 3D structures using NMR data. We would never have been able to test the idea, which came up in a phone conversation several months ago, without all of your contributions.

Today I spoke at the AidsVaccine07 meeting about our work on designing vaccines. Scientists who have been working on this very challenging problem for many years are I think excited about our approach as it is something that hasn't been tried before and makes sense conceptually. While we are still far from a vaccine, our initial results with collaborators at the NIH are promising. I spoke to a reporter from the Wall Street Journal after my talk, and I think she is interested in writing an article on rosetta@home and HIV vaccine design.

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Congratulations! Your collective results on structure prediction, protein structure refinement, and solving the X-ray crystallographic phase problem with rosetta@home were just yesterday accepted for publication as a research article in the journal Nature which many of you can find at your local newstands (I'll post here when the issue appears in print). As those of you familar with scientific publishing are certainly aware, Nature is probably the most widely read journal in the natural sciences, and only one or two research articles are published in any issue (almost all are shorter letters), so your work will reach a very broad audience and have exceptionally wide impact.

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As almost all of you know, we had the largest computer failure in the history of Rosetta@Home last Tuesday. Not only were we unable to make use of your valuable contributions, but also all of our internal computers were down as well, so the graduate students and postdoctoral fellows in my research group have had their resaearch projects stalled out. Quite a disaster! Fortunately, Keith and Chance, the computer gurus who keep Rosetta@Home and the group cmputer clusters running, are absolute pros, and they have worked miracles to get the project back on line even with this catastrophic failure. (to give you an idea, whenever anybody at the UW wants to set up a computer cluster or has any question to do with large scale computing hardware, Keith and Chance are the people they go to to find the answer). From Keith's most recent email, it appears that things are not fully back to normal, but hopefully we will be running as strong as ever very soon. In fact, as I will post once we are back up to speed, we have a very pressing scientific challenge we will need all of your help on!

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Now for the good news!

As many of you will remember, you started seeing RNA molecules folding on your screensavers in addition to proteins about 9 months ago. Rhiju had generalized the Rosetta folding methodology beyond proteins to RNA which also adopts folded functional structures in addition to being a critical component in the reading of the genetic code inscribed in DNA. Using your computers, he tested his new RNA folding protocol, and the exciting results he obtained he reported in a paper that was submitted to the proceedings of the national academy of sciences (PNAS) several months ago. The paper was accepted with rave reviews, and has just appeared in print.

It is the policy of the PNAS journal to highlight for each issue the papers of exceptional interest. Your work, as reported in Rhiju's paper, is the major highlight of the issue of PNAS that just appeared! You can read about this months highlights in PNAS at

http://www.pnas.org/misc/highlights.shtml

In this paper, as in all of our papers (quite a few by now!) that have relied absolutely on your contributions, we have thanked all rosetta@home participants and cited by name those contributors who found the lowest energy structures. You can see the list at

http://www.pnas.org/cgi/data/0703836104/DC1/7


Thank you for your contributions, and we look forward to many more important scientific advances with your help at rosetta@home in the next year!

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We have made huge progress with the interactive video game version of rosetta. We are on our sixth trial so far, with many improvements being made at each step. in the most recent trials, a subset of the people who have tried have become hooked and played (competitively) for many hours in a row. our goal now is to increase the fraction of people who get really into the game by adding animations and other information at the beginning to help guide people starting to play for the first time.
Within the next month I will be asking for volunteers for a more general trial. The reason for all of the trials is that we want to have the game really perfect before it goes fully public. Again, the two main goals are (1) educational--I'm convinced that people playing the game will gain a huge amount of insight into what biomolecules are and how they work and (2) research--we think people playing the game may be able to find much lower energy structures than the computer working on its own. time will tell!
On the science side, we are just completing two manuscripts describing landmarks in molecular biology: the design of novel enzymes (using computational protein design and rosetta@home) that catalyze chemcial reactions for which there are no naturally ocurring catalysts. (perhaps one of the experts among you can explain what this means on the "discussion" thread). I presented this work at two recent scientific meetings and people were pretty blown away. This opens the door to creating new catalysts for all sorts of chemical reactions that are difficult currently or require toxic or environmentally unfriendly reaction conditions.

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There is a news article describing all of your work (plus a strange picture) at
http://www.nature.com/news/2007/071016/full/449765a.html. the print version should follow
in a week or so.

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The rosetta@home research paper is now in print in the Nov 8 issue of Nature, and there is a brief discussion related to rosetta@home in the news section of this issue.

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We have been working hard on a new streamlined version of rosetta which will soon be running on rosetta@home. there are so many developers of rosetta that the code grew very large and somewhat disorganized, and several members of the rosetta develpment community took it upon themselves to write from scratch a modern completely object oriented version. many others have joined in more recently, and the new version is now almost up to speed. we can tackle some new problems with this new code, as well as all of the old ones, so we will be gradually transitioning over in the next six months.

among the new things to come in the relatively near future include virtual drug screening by large scale docking of small molecules onto protein targets. accurately docking even a single small molecue onto a protien target is fairly computationally intensive, so if we want to dock 100 or 1000 possible drug candidates onto a protein target large scale computing will definitely be critical.

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I aplogize for the rosetta@home site being down mid last week. Fate was against us: just as David K. was going in for surgery on his arm, a problem arose with the job feeder; normally David would have caught this immediately but it took the rest of the team a couple of days to figure out what was happening and how to fix it. Thanks to Rhiju for fixing the problem in the end.

We have a very early and preliminary version of the rosetta game ready for testing and will soon be looking for volunteers. If one of you can collect email adresses of people interested in trying it out, I'll post instructions on who to send it to later this week. We don't want to make it completely public until all the bugs are out and it is truly fun to play!

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I'm delighted by the early reviews of the rosetta game, which you can sign up to play and test as organized by the terrific rosetta@home moderators at
https://boinc.bakerlab.org/rosetta/forum_thread.php?id=3789

We still have some polishing to do before the game goes public--we want it to be as good as possible by then! The current plan is to use a "viral" distribution model for the next several weeks in which people testing the game can invite friends to play as well, an advantage of this is that the friends can go to the person who invited them to get up to speed on how to play, strategies, etc.

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You can now read about a very exciting collaborative research project we (and you) are involved in which aims to use computational protein design to repair mutations in genes which cause disease. This is a collaboration between basic science researchers and clinicians at Children's hospital and the Fred Hutchinson Cancer research center in Seattle who treat patients with these diseases. The url is:

http://research.seattlechildrens.org/centers/immunity_vaccines/ngec/

This is one of a small number of "Roadmap" projects recently funded by the NIH which apply cutting edge basic research to work towards novel cures for diseases.

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