Dartmouth College Scientists need your help with a Brain Cancer-related puzzle!
Having been a (novice) Foldit player myself I was aware of the potential utility of this powerful computational platform in modeling proteins even before I joined my current laboratory. When the topic of needing a structure for our protein came up in a meeting, of course Foldit was on the top of my mind. We hope that the players of Foldit can help us uncover the structural basis of Id2 activity and thereby inform the development of novel targeted therapies for Glioblastoma.
Inhibitor of DNA Binding 2 (Id2), a helix-loop-helix (HLH) protein, inhibits normal gene expression by binding and suppressing other transcription factors. Recent data from our laboratory show Id2 is a key protein in the pathogenesis of a subset of aggressive brain cancers (Glioblastoma). The structure of the HLH domain of Id2 is well characterized. However, the unknown terminal regions are very important for regulation of the protein. Having the structures for the terminal regions will help us understand how the regulation of Id2 alters its structure and function. This will help us identify regions of Id2, or proteins that
interact with Id2, which are important for degradation. We could use this knowledge to develop drugs that promote the degradation of Id2 to treat Glioblastoma.
Try out our Brain Cancer-Related Phosphorylated Id2 puzzle here. Thanks!( Posted by cymbal_king 78 2765 | Thu, 05/29/2014 - 16:06 | 1 comment )
Wiggle Power Results
We recently posted a bunch of De-novo puzzles where the "High Wiggle Power" option was disabled and hopefully the results from those puzzles will explain why we've given High Wiggle Power a time-out during CASP11.
Below are RMSD plots for De-novo Freestyle 36 puzzles 864: Low Power & 868: High Power. The green dots represent your many different Foldit predictions, and for all these RMSD plots, you want to be as close to the left as possible (an RMSD=0.0 would be a perfect match to the native).
You can see that the top-scoring Foldit solution (the lowest Rosetta energy) doesn't change much between puzzles RMSD-wise. So although the high-scoring Foldit solution for puzzle 868: High Power was 9,208 (compared to 9,098 in puzzle 864: Low Power), it is not any closer to the native.
In general (and this was the case for all the Low Power/High Power plot comparisons) although the scores were better in the High Power rounds, the models were not any more accurate. We hypothesized that this could be happening because we allowed you to load in solutions from the Low Power rounds, and therefore the High Power round was mostly "drilling" down the energy landscape of those previous models (since doing that would obviously improve the in-game score!).
This is why for 880: De-novo Freestyle 38: High Power we did not let you load in solutions from the previous Low Power round.
You can see in the plots below that this High Power round had fewer green dots, but unfortunately the results are actually much worse than the Low Power round:
On the left, 876: De-novo Freestyle 38: Low Power has a very nice plot where the top-scoring Foldit model is one of the left-most points. This is not the case on the right, where the top-scoring Foldit model from 880: De-novo Freestyle 38: High Power is much further from the native than in the Low Power round.
The exciting news, however, is that the results from the Predicted Contacts rounds have been very promising!
You can see this below for the De-novo Freestyle 37 puzzles:
On the left, the top-scoring solutions for 867: De-novo Freestyle 37: Low Power are not the left-most points on the plot (they are quite far away from the native topology) but given predicted contacts, your results on the right for 875b: De-novo Freestyle 37: Predicted Contacts look great!
So we are looking forward to the Contact-assisted CASP11 targets, and hopefully this post explains why we'll give High Wiggle Power a rest during CASP11. The CASP season is long and busy enough that we don't want to waste your time gaining Foldit points, but not getting more accurate solutions!
Lastly, Seth and I wanted to thank all of you in the DC area who stopped by when we presented Foldit (and debuted nanocrafter) at the 3rd USA Science & Engineering Festival.
Next time we promise to give everyone a little bit more advanced notice, and we'll make sure to have a camera ready from day 1. At least we managed to snap a photo with Galaxie on the last day:
Thanks for all your hard work, everybody... and keep up the great folding!( Posted by beta_helix 78 2765 | Tue, 05/13/2014 - 16:10 | 9 comments )
Visit the Center for Game Science's Newest Projects!
While we know you're already hard at work on the latest CASP competition, we thought we'd take a moment to talk about two new projects from the Center for Game Science: Nanocrafter and Flow Jam. These games build on what we’ve learned over the years working with you on Foldit, applying those lessons to brand new domains of scientific discovery.
Nanocrafter allows players to assemble molecular structures out of DNA. Novel designs in synthetic biology, as this new field is called, could benefit vaccines, cancer research, and more. Recently announced at the Games for Change conference at the end of April, Nanocrafter already has a rapidly growing community of builders. Help shape this new community and be sure to follow our alerts on Facebook and Twitter for the newest coverage!
Flow Jam, part of the Verigames project, is a novel approach to proving large and complex software programs free of certain errors. All newly developed software requires time-intensive testing by computers and human experts before the software can be considered reliable. If this sounds interesting to you, head over to the page and try it out, pop by the official forums, and follow our Facebook and Twitter accounts on that game for the latest news.
There’s never been a better time to contribute to scientific discovery and advancement through gaming! As veterans of Foldit we look forward to hearing your feedback on our newest efforts.( Posted by inkycatz 78 2765 | Mon, 05/05/2014 - 20:26 | 3 comments )
Welcome our new Community Liaison!
To start your week off, we'd like to take a moment to introduce our new Community Liaison, Nova "inkycatz" Barlow. She'll be working on Foldit in addition to other Center for Game Science titles.
A well-established community advocate, Nova's most recent work includes Kodu Game Lab and Project Spark at Microsoft. For those fans of our IRC channel, you may have already spotted her lurking around late last week getting up to speed. She's thrilled to be joining this established community of folders and can't wait to hear your thoughts.
Feel free to say hello and offer your best folding tips!( Posted by inkycatz 78 2765 | Mon, 05/05/2014 - 20:13 | 2 comments )
Predicted Contacts and The Contact Map
It's time to introduce our newly redesigned Contact Map. We've completely redesigned the Contact Map in order to better tackle the contact guided structure modeling targets in the CASP competition. We'll frame these targets as Predicted Contact Puzzles in Foldit.
Our original Contact Map was designed for the legacy "Exploration" Puzzles, and needed to be upgraded badly. With that in mind, we've recreated the Contact Map to deal specifically with the Contact Predictions that we will see in CASP. It should scale better with larger proteins (Veteran users may recall some puzzles where the old map would take up most of the screen). This should let the Contact Map handle any proteins that Foldit itself can handle.
The new Map should be much clearer and easier to use. In addition, it should provide some new functionality that should come in handy during CASP!
First - what is a predicted Contact? A predicted contact is a prediction that two Residues in the protein will be close together, or "in contact". They wont actually be touching (this would be clashing), but will still be fairly close.
Each contact has a "weight" associated with it, which is a measure of the likelihood that the residues involved actually form a Contact in the native protein. The higher the weight, the higher the likelihood. Note that this means some contacts can be incorrect, so a decision has to be made as to which contacts should be pursued.
In Foldit, we are going to try several different approaches to rewarding players for matching predicted contacts. Up until now, we've been re-using the Exploration Puzzle system, which lead to a lot of confusion.
No longer! - The Contact Map is now set up to be independent from the scoring method used to reward matching contacts.
This gives us the ability to run Contact Puzzles in 3 different ways:
* Purely as a visual guide, with no reward for matching contacts.
* In combination with a Filter that will give you a small bonus for matching contacts.
* In combination with puzzle Constraints, which will penalize the score of structures that are missing high-likelihood contacts.
Predicted Contacts are a great domain where players have the potential to succeed where computers have failed, and we've designed the Contact Map to try to give you the best shot at it!
So without further delay, below is a visual guide (You might call it a "map"!) to the Contact Map:
The Contact Map
1. This shows the residues involved in the contact that you are currently hovering over with the mouse.
2. This shows the weight of the contact that you are currently hovering over with the mouse.
3. These black dots show contacts which your current protein model has.
4. This button will clear the selected cells.
5. This button will add a band for each selected cell. The band will be between the two residues involved in the contact, and will have default length and strength. In the future, we plan to set the strength and length based on the contact prediction.
6. The diagonal represents the backbone of the protein. The color of the diagonal indicates the secondary structure for that section of backbone. In this case, it is red, which corresponds to a sheet.
7. An empty color on the diagonal corresponds to a loop.
8. Blue on the diagonal corresponds to a helix.
9. Green cells are predicted contacts. A brighter green means a higher weight, and a more likely contact.
10. The highlighted and outlined regions are the selected cells. When you select a cell, you will see a red or green band on the protein model itself, with color indicating whether you have satisfied that contact or not. You can select a cell by left clicking the cell.
11. Clicking and dragging this bar will allow you to re-size the contact map.
12. The map will highlight the contact you are currently hovering over with a vertical and horizontal bar. Additionally, you will see a yellow band on the protein model itself, which links the two residues involved in this contact.
The Contact Map also allows you to zoom with the mouse wheel. While zoomed in, you can also pan over the map by right clicking the map and dragging.
We've just posted a puzzle which features the Contact Map, which you can find here: http://fold.it/portal/node/997597
We hope you enjoy the new Contact Map, and we're looking forward to seeing how you all use it during CASP!( Posted by jflat06 78 1041 | Wed, 04/30/2014 - 20:41 | 5 comments )