Upcoming ligand binding puzzle!
We have an upcoming Foldit puzzle where we are again attempting to bind a biotin molecule! I hope you all didn't miss it too much! In this puzzle, we have introduced indicators to help the players make more ideal hydrogen bonding angles. For this specific ligand, we're asking for 3 hydrogen bonds to be made with the oxygen at the "business end" of the ligand. (The side that is directed into the scaffold). Here is an example of what the near ideal angles should look like:
We aren't so much interested with hydrogen bonds being made to the linker portions of the ligand. (Everything that is not at the business end of the ligand) But the more the better!
I hope you guys can come up with some interesting solutions! If you can make a good enough solution, we'll make the protein and tell you if it works! (Should take about a month from time of order) And if it works, we'll put you on the resulting paper!( Posted by austinday 87 1969 | Fri, 03/05/2010 - 23:03 | 2 comments )
First alignment puzzle results!
We've been looking at the results from the first alignment puzzle, and they are definitely encouraging! In this case, we know the native (the protein structure we are trying to find). Here's an image with the template from the puzzle in red, the native in green, and the top scoring structure (produced by TheGUmmer and Madde) in blue. So the question is, can we get from threading the red template to the green native?
You can see that the main difference between the red and green structures is that loop on the left side. But the blue solution structure has gotten much closer to the native! The alignment that was used to make the solution was:
For comparison, The starting alignment for the puzzle was:
So they're pretty similar, but sometimes small alignment changes can make a difference. Excellent work!( Posted by Seth Cooper 87 1969 | Sun, 02/28/2010 - 22:29 | 0 comments )
New Comparative Modeling Tools for Structure Prediction
This week we have released some new tools in Foldit for structure prediction. The update comprises several tools and some new levels that teach you how to use these tools. The rest of this blog post is to try and give an overview of why these tools are useful in structure prediction.
Often when we try to predict the structure of a protein, that protein has a similar amino acid sequence to one or more proteins of known structure. These known structures are called templates, as they can be used as starting points for predicting the structure of new proteins. We call this approach to structure prediction comparative modeling, as it is based on comparing a protein sequence to existing structures in order to build models. These tools are based on the same code that is being used within the Baker Lab for comparative modeling and structure refinement, so that comparisons between automated Rosetta protocols and manual structure prediction using Foldit are more fair now.
We compare protein sequences using a tool called a sequence alignment. A sequence alignment is simply a mapping of residues from one sequence to another. For comparative modeling the sequence alignment tells you which residues are analogous between the query sequence and the template sequence. In the context of comparative modeling, the sequence alignment tells you which sections you should copy from a template structure and which residues you should try to optimize more freely. By manipulating the sequence alignment, you can get different starting structures which you can then refine using the existing tools in Foldit.
Many of the successful predictions from CASP8 were comparative modeling puzzles, but sequence alignment for these targets were done by scientists in the Baker Lab and left fixed for the Foldit players. With the latest Foldit tools for comparative modeling, you can manipulate the sequence alignment and use it to generate models interactively. Our hope in releasing these tools is that by being able to explicitly manipulate the sequence alignment and refine the resulting models, the players can both understand structure prediction better and build good comparative models of proteins using Foldit.( Posted by tex 87 1969 | Tue, 02/23/2010 - 20:01 | 0 comments )
Nature paper submitted
as of last week, we submitted the Nature paper. We think it has some very exciting findings, all of which are trying to uncover the amazing process that happens through game play. We analyzed things from many different angles producing some very interesting figures. We'll share them with you as soon as we hear from Nature. One interesting thing about our paper is that in the author list we added "and < 100,000 Foldit players". Surely the largest author list ever, but we're still not sure if Nature will balk at that format.
At this point three things can happen: they reject the paper, they reject it with specific suggestions on how to strengthen the results (which implies subsequent resubmission), or accept. I am guessing we should know in a month or so. Fingers crossed.( Posted by zoran 87 1969 | Thu, 02/04/2010 - 23:03 | 2 comments )
Digital media and learning competition: help needed
As you know, for a while now we have been excited about the educational possibilities of foldit. Every week we get a new set of requests to setup puzzles as class homework at some university.
We plan to spend some of our time to make these things easier. Recently, we've submitted a proposal to extend foldit to become a biochemistry tool for middle- and high-school students. To read about it and help us win the grant, please go to the below link and post a comment: the open-to-public feedback session will soon be closed, so time is limited.
Thanks for your help.( Posted by zoran 87 1969 | Mon, 02/01/2010 - 17:30 | 2 comments )