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Citizen Science Day Heroes

It's Citizen Science Day and the fine folks over at the Human Computation Institute together with SciStarter have put together an event called the CitSciDay HERO Challenge. Players go around and try out some cool citizen science games and earn badges. You may have guessed it, Foldit is involved this year! There are likely to be some fresh faces in chat from people coming by to earn their badge and try Foldit on for size. If you want to check out the event (or claim your Foldit badge!) check out the blog post here.

(Sat, 04/14/2018 - 16:47  |  0 comments)

Developer Preview Release Soon

Hey everyone,

We're going to be pushing an update to the developer preview soon with the following fixes and features:

General:
* Added the Pin Tool - this allows players to have greater control over where the changes to the protein backbone are rooted. To access, go to the view options and check 'Show backbone pins' (off by default, and not shown when 'advanced gui' isn't enabled). A pin will appear over each piece of protein representing where the piece is rooted. Left click and drag to move it, right click to keep the piece from moving. You can find a quick demonstration here.
* Added additional info to Foldit's crash reporting system to better track down bugs.
* The Ideal loops gallery has been removed from the RamaMapPanel. The Rama map also now shouldn't take up processing resources when it not visible.

Bug Fixes:
* Sound has been re-enabled.
* Fixed some small memory leaks.
* Improved performance for several visualizations.
* Various fixes and improvements for drug-design related tools and scoring.

As a final note: over the next few weeks we are planning to test out some experimental features in the intro puzzles. You might notice that new or different features are available in some of these puzzles. This should not affect the science puzzles. If you are an instructor using Foldit and would like to have the standard features for your class, please contact us.

(Wed, 04/11/2018 - 00:56  |  1 comment)

Foldit at USA Science and Engineering Festival

Foldit will have a booth at this weekend's Science and Engineering Festival in Washington D.C. Admission is free, and anyone in the D.C. area should stop by and meet beta_helix and Seth Cooper in the Walter E. Washington Center, April 7-8.

(Sat, 04/07/2018 - 00:34  |  3 comments)

Aflatoxin Challenge Update

Foldit Community, we are ready for an Aflatoxin update! Thank you for all your efforts in designing the first round of designs to combat aflatoxin. To date we have had hundreds of players design >400,000 structures! There is a lot to choose from and it has been a fantastic way to start off this effort. Players have been incredibly creative, and have engineered exciting new molecular interactions that truly have the potential to stabilize the aflatoxin hydrolysis transition state we provided in the models. Two examples are below: the first is a pi-pi stacking interaction between a tryptophan and the conjugated ring system of aflatoxin AFB1 (left, Figure 1). If the designed protein is stable enough in this state to provide this interaction in the physical world it would almost certainly position aflatoxin in a manner poised for enzymatic hydrolysis. The second interaction is a classical hydrogen bond with a ketone group (right, Figure 1). Again, these energetically favorable and strong interactions will provide the physical properties needed to stabilize aflatoxin AFB1 in a manner ready for hydrolysis by the naturally occurring catalytic core of the enzymes. We look forward to seeing more of these interactions in subsequent rounds!


Figure 1. AFB1 interactions in Foldit player designs. In both images the white structure is the native enzyme (starting structure), and the green is a Foldit player design. Left, a double mutation accommodated by some backbone movement enabled a pi-stacking interaction between tryptophan and AFB1. Right, a single mutation and backbone change introduce a hydrogen bond with the ketone group on AFB1. Keep making changes! And remember that it is not only important to interact with AFB1, but also to stabilize the new protein structure to reinforce the AFB1 interactions!

Experimental Charactization

On the experimental front we are excited to announce that we have transferred all methods into a microtiter plate format and have tested the first 100 GeneStrings from ThermoFisher designed by players (Figure 2). These were selected on a variety of factors (~30 of the top scoring based on overall score; ~30 based on top AFB1 energy with above average overall score; best score of 20 players sorted on best scoring designs; all of the player Scientist Shares). While the process from design to data was seamless, unfortunately all of the data was negative (i.e. none of the designs degraded aflatoxin). We are going back to this first round and re-evaluating how we picked designs, as well as going back and refining some of the designs we thought were most interesting ourselves, however in the meantime we want to get another round of puzzles going. Don’t lose hope! We expect this will require several rounds of design as we optimize the puzzle and solution selection parameters, as well as start to prepare a few new scaffold proteins to try. But we are confident we will find something in the next few rounds and we appreciate your diligence and efforts in helping solve this global issue!


Figure 2. Workflow from Foldit to experimental data

Next Puzzles

There was great feedback from the community about the original puzzles and we plan to adjust the next puzzles based on this feedback. Most importantly, we plan to trim some of the frozen protein regions, so you can deal with a smaller puzzle and focus on the regions of interest. We may also upweight the ligand scoring, to encourage more interactions with the ligand. Although some players have requested the ability to move the ligand around the binding pocket, we will continue to keep the ligand fixed in place; the ligand's orientation with respect to the catalytic residues is critical if we want the reaction to occur!

We will continue to update you as we go, but we're off to a strong start! Check out Puzzle 1497: Aflatoxin Challenge: Round 5 now!

( Posted by 81 2386  |  Wed, 03/14/2018 - 23:04  |  6 comments )
2

New Update! (REQUIRED)

Hey everyone,

We've just posted an update to the game that improves our biochemistry software under-the-hood.

This update is a major change to the way the game scores your proteins, so you will need to update your software in order to see or play any new puzzles.

There's a great blog post about some of the specifics of the update here.

A huge thanks to the players who helped to test this update in the 'experimental' build!

(Tue, 03/13/2018 - 18:20  |  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