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This is the place where we will describe some of the outcomes and results of your folding work, provide a glimpse of future challenges and developments, and in general give you a better sense of where we are and where foldit hopes to go in the future.

Improvements in Foldit designs

Hi all, I wanted to share some exciting results we've gotten from folding predictions of Foldit designs!

As many of you know, after a design puzzle closes we submit a selection of Foldit player designs to the Rosetta@home distributed computing project. Rosetta@home distributes your design sequence to 100,000s of home computers all over the world, so that each computer can calculate a prediction about how that amino acid sequence might fold up. This huge dataset of predicted structures tells us a lot about the weaknesses of a design, making this the most rigorous test available to validate designs before we construct the actual proteins in the lab.

The plots below show Rosetta@home datasets from two Foldit monomer design puzzles. Each red dot represents a different predicted structure, and is positioned according to its RMSD (root-mean-square deviation in Cα position; closer to 0 means closer to the designed structure) and its score (a calculated potential energy; more negative score means a more stable structure). What we like to see is a "funnel" running from the upper-right to the lower-left of each plot. This indicates that predictions very different from the design structure are unstable, and that more similar predictions are more stable.

The top-most plot represents the top-scoring solution from Puzzle 798, which we ran in October of 2013. Note that the closest prediction has an RMSD of >2 Å, meaning that no prediction even got close to the designed structure. Furthermore, the closest predictions were not even the best-scoring; the lowest-energy prediction for this structure has an RMSD of 7 Å, representing an entirely different fold.

The lower three plots represent the three top-scoring* solutions to Puzzle 854, which closed a couple weeks ago. Each of these plots shows that the lowest energy prediction is <1 Å RMSD from the designed structure—an incredible result (the first funnel is stronger than many of the designs we come up with in the Baker Lab). Perhaps even more exciting than the quality of these folding funnels is the fact that they were derived from the best-ranked Foldit solutions, whereas in previous puzzles, scientists in the lab have been able to identify poor-ranking designs that fold better than the top-ranked solutions. These are all very exciting results, and a batch of designs from Puzzle 854 is being fast-tracked to lab production presently.

We appreciate all the effort that our Foldit players have invested in adapting to the recent changes in gameplay, and a big thank you especially goes to all those players who have been helping us troubleshoot and fine-tune the latest design tools. Note that we are still working to slim down the client and optimize these tools to be efficient as possible. Likewise, there is still plenty of room for improvement on the side of the Foldit players (we'd love to see some more beta-sheet designs** :P). Stay tuned for results from the lab!

*These are the three top-scoring designs that did not come from the same group, since players from within a group often have very similar top-scoring solutions. These designs are all significantly different from one another.
**We're working on this as well. Foldit is inherently biased towards helices, so this will be a bit of an uphill battle.

( Posted by  bkoep 83 1247  |  Tue, 03/25/2014 - 06:07  |  9 comments )

Auto-Wiggle Power and Idealize Secondary Structure

We're introducing several new features soon, and we're here to give a brief description of what they do.

Auto Wiggle Power

We've heard requests by many players to make Low Power Wiggle the default. Our reasons for not making this change might not be obvious. There are tools in the game that allow you to introduce unideal peptide bond lengths and angles, and we want the default behavior to be capable of resolving these issues. Low Power isn't capable of addressing these issues, but Medium Power can.

However, as many of you have noticed, there are a couple of problems with Medium Power Wiggle. The first is that it is slow. This is because Medium Power Wiggle modifies bond lengths and angles for every peptide connection in the protein. Thus, there are more variables for Wiggle to try changing, which takes more time. The second is that since Medium Power Wiggle has more freedom of which variables to change, it can find better shapes and get 'stuck'.

We'd love to have the unideality-resolving power of Medium Power with the speed and looseness of Low Power - that's the purpose of Auto-Wiggle. When you start a Wiggle, Auto Wiggle Power figures out the bare minimum of extra computation to resolve the unidealities, instead of just including all bond lengths and angles like Medium does.

The result is that instead of adding ~400 extra degrees of freedom like you would with Medium Power, you're now only adding on average ~4 with Auto Wiggle Power. And if you have NO unidealities, it will function identically to Low Power Wiggle.

We hope you like it!

Idealize Secondary Structure

Another request we've seen is to make forming Helices and Strands easier.

Since Secondary Structures are so critical as building blocks for proteins, we agree! Our current tools for forming a perfect helix or strand are Rebuild and Tweak. Neither of these tools is particular good at that task, so we've decided to give you a dedicated tool: Idealize SS.

Idealize SS turns a helix or strand into a perfect helix or strand. Like Idealize, it simply sets these values, so there will be global changes even when run on a local region. If you want to prevent this, you'll have to use cuts.

Idealize SS is available in the right-click menu of the Original Interface or by any non-empty selection in the Selection Interface.

( Posted by  jflat06 83 1089  |  Thu, 03/06/2014 - 20:51  |  6 comments )

Scientist Feedback on the Hotspot Finding Puzzles

     Hi, folks. I just wanted to write a quick note thanking everyone who has been playing the hotspot finding puzzles. Players produced some very neat designs in both the SOD1 and Ebola puzzles. The Ebola one particularly has yielded some great starting points for design, and we currently are extending players' designs using Rosetta to try to make peptides and proteins that neutralize the Ebola virus. I was also very interested to see common features emerging in the diverse designs. Many players seemed to find, independently, that there was a "shelf" in the Ebola glycoprotein that could accept an amino acid with a flat side-chain, and that this was was adjacent to a "chasm" that could accommodate something with a long side chain. These players created designs accordingly with many different "shelf/chasm"-filling pairs. This is the sort of insight that only human intuition can provide. Automated algorithms have a very hard time discovering patterns like this.

     Thanks also to those who have been using the "share with scientist" button. In both puzzles, there were some very interesting designs that were shared. I noticed that in the SOD1 puzzle, a few clever players noticed the two cysteines (cysteine 111) located on opposite sides of the dimer interface, and created peptides with two cysteines that could form disulfide bonds to both of these amino acids, thus covalently linking the dimer. These designs weren't the highest-scoring (the scoring function isn't smart enough to recognize this as a good design), but they're definitely useful designs, and they're exactly the sort of thing that the scientists want to see. Good idea, and good work!

     We've got a lot more targets for which we need hotspots, so if players are enjoying these puzzles, we can post more. Feedback on this hotspot-finding puzzle format is welcome, too. It's our hope that these puzzles will give us the starting point that we need in order to allow us to design drugs to treat some very nasty diseases, so your participation is greatly appreciated.

          --Vikram K. Mulligan

( Posted by  v_mulligan 83 2645  |  Thu, 02/27/2014 - 08:04  |  7 comments )

Foldit Remote Control

Embedded Video: 

Hey everyone,

Get ready for a new way to play Foldit!

Over the past couple of months, we’ve been working on a way for Foldit to be available on more platforms. As you are aware, the game is highly computational in nature, constantly being updated to use the latest scientific tools to most accurately score proteins. This represents a challenge in bringing the game to low power, portable devices. The solution that we have come up with opens up the possibility for Foldit to be played on many devices, without affecting one aspect of the game: using the best computational tools available.

Say hello to Remote Control, a streaming system that allows you to play fully featured Foldit on your tablet or smartphone.

How does it work? Essentially, Remote Control connects the computational power of your computer to your smartphone or tablet. Run Foldit on your computer, then open up the new Remote Control panel under the social tab to open up your computer for connection. Download the Foldit app on your Android tablet or smartphone (Android is our first platform, iOS is not currently supported) and type in the IP address of your computer to connect for a complete Foldit experience.

Why did we decide to implement Foldit on Android as a streaming system? This opens up several possibilities beyond Android. The overhead is less for bringing remote play to more platforms in the future. There is the opportunity to natively stream Foldit to multiple devices at once; think next-generation classroom interactivity, with an entire classroom able to view their teacher’s protein on their own device. All in all, it eliminates most barriers of porting to new platforms, and gives us more flexibility to focus on revolutionizing the gameplay and science itself, rather than the platform details.

Now more than ever, we would love to hear your ideas and feedback! Check out the preview below, and stay tuned for the upcoming release.

( Posted by  jeffpyke 83 2645  |  Tue, 02/25/2014 - 03:12  |  11 comments )

David Baker on the benefits and frustrations of NewChapter

Embedded Video: 

Dr. David Baker of the University of Washington's Institute for Protein Design addresses Foldit players to talk about the importance of the changes in the NewChapter release of Foldit, and to acknowledge the frustrations that some players are having with the game during the transition.

( Posted by  v_mulligan 83 2645  |  Sun, 02/09/2014 - 23:11  |  1 comment )
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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Microsoft, Adobe, RosettaCommons