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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.

Exploration Puzzle 1

We're introducing a new puzzle today. It's also a new type of puzzle: one where you have to explore far from the starting structure. You've had a preview of this in the exploration map, and this map (Exploration Map in the Social tab) will be an important tool for these new puzzles.

Exploration MapExploration Map

The exploration map shows a point for each protein structure you make: whether it's by pulling the structure, wiggling, shaking, or rebuilding. Each point has two values associated with it: the Foldit score and how different the protein is from the starting protein. This map shows the protein structure "landscape": the different types of shapes it can take, and the score Foldit gives each shape. You might be exploring a new region on the map that initially gives you a worse score, but by working hard in this new region, you may find the correct shape and get the highest score.

Many of you have probably noticed this in an intuitive sense: when we look at the top scorers for many puzzles, we see some of the most bold explorers: people who explore new regions, and then work hard to improve the score in these new regions.

In evolver puzzles, you start with a protein with some score. Before you get a ranking in the puzzle, you must improve the score. In these new exploration puzzles, you must change the protein significantly before you can get a ranking. Foldit also remembers the original structure, so your score won't count if you go back to a similar shape to the start. Keep in mind that for these exploration puzzles the red dot on the exploration map will represent the starting structure's score (even though you are unable to reach that score without changing the structure significantly).

Rosetta sometimes has problems exploring this landscape. We want to see if we can learn from human players how to explore more effectively. So be bold, be creative, and have fun!

( Posted by  Seth Cooper 81 2394  |  Sat, 09/12/2009 - 00:08  |  0 comments )

Cover the Ligand

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As environmental impact becomes an increasing concern for chemical manufacturing, the idea of using enzymes in environmentally friendly conditions to catalyze chemical transformations instead of traditional chemistry is becoming increasingly important. Unfortunately, naturally occurring enzymes only catalyze a subset of the reactions that are readily available to the synthetic chemist. Therefore engineering enzymes to catalyze novel chemical reactions is an area of great interest. To address this we are using the computational tool ROSETTA to engineer an enzyme capable of catalyzing one such reaction: an intermolecular, stereospecific Diels-Alder reaction. While no clear examples of this reaction have been shown to occur in nature, it is one of the corner stone reactions used by synthetic chemists to form carbon-carbon bonds and received a Nobel prize in 1950 ( While popular with synthetic chemists, this reaction often falters due to the large number of different products that can be formed when bringing two molecules together. With an enzyme we can control the way the two molecules come together during the reaction, therefore we will be able to catalyze the formation of a single product. We hope that this novel enzyme and more like it will introduce a new class of environmentally friendly chemical reactions available to the biochemist’s tool bench and lead to the creation of new drugs, commodity chemicals, and more!

The “Cover the Ligand” Puzzle is one of the Diels-Alder enzymes we are currently engineering. Unfortunately only half of the ligand is covered making it so our initial design is a weak binder. With your help we would like to increase the size of the loops surrounding the ligand, allowing additional amino acids to touch the ligand, which should result in an increase of this enzymes catalytic efficiency.

Your designs will be ranked based on score and number of additional contacts made to the ligand. The most promising of your designs will then be synthesized and experimentally tested in the Baker lab. We look forward to seeing all of the exciting new solutions you come up with!

( Posted by  siegeljb 81 2394  |  Tue, 08/25/2009 - 21:15  |  2 comments )

Foldit scripting preview

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We've started working on adding Lua scripting, and here's a very rough preview of what it looks like now. This is just in a command line window, but there will also be support for scripts in the cookbook.

What do you think? What kind of API would you like to see? Let us know in the comments!

( Posted by  Seth Cooper 81 2394  |  Fri, 08/21/2009 - 21:04  |  10 comments )

Poll: Outlines

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We recently added an option to turn the outlines on the protein structure on and off. This was initially for performance reasons, but it has also come up that the protein may look better without them as well. So, here's a poll to decide what we should do with the outlines, let us know what you think!

( Posted by  Seth Cooper 81 2394  |  Fri, 08/21/2009 - 19:07  |  1 comment )

Design of inhibitors update

The results from the inhibitor design puzzle have come in and it appears that many of the players fully identified all of the hot-spot residues - those are the residues on the inhibitor that are crucial to inhibition in the natural inhibitor. This is very impressive because getting these hot-spot residues correctly requires a combination of tools that Rosetta provides, including sidechain redesign and minimization.

We will next provide several other puzzles similar to this one, where we know what the hot-spot residue identities are, but we shaved those off and you can try to recapitulate them. The first in this set of puzzles is the structure of human growth hormone bound to its receptor.

Following a few of these puzzles we would like to ask for your help in improving our designs for a variety of protein targets. I'm looking forward to your participation and am eager to see what design possibilities you could uncover that we miss.

( Posted by  sarelf 81 2394  |  Tue, 08/04/2009 - 23:30  |  0 comments )
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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