Selection Mode Feedback
A couple months back, we released an update that allowed you to try out a new interface that we have been working on that was based upon selecting portions of the protein and perform actions on that selection. (Review of that update can be found at http://fold.it/portal/node/986573). We're interested to hear what those who have tried out this new interface think about it, and whether or not it is or could be an improvement over the existing interface.
Please comment with your feedback, or simply vote on this post based on whether you like the new interface or not.( Posted by beenen34 76 2107 | Thu, 10/08/2009 - 22:58 | 4 comments )
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.
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 76 2107 | Sat, 09/12/2009 - 00:08 | 0 comments )
Cover the Ligand
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 (http://en.wikipedia.org/wiki/Diels%E2%80%93Alder_reaction). 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 76 2107 | Tue, 08/25/2009 - 21:15 | 2 comments )
Foldit scripting preview
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 76 2107 | Fri, 08/21/2009 - 21:04 | 10 comments )