Closed since almost 7 years ago
Advanced Overall DesignNote: Due to some recent server problems, the puzzle expiration will be extended 24 hours. The puzzle will close on March 26 at 23:00 GMT.
Note: This puzzle replaces Puzzle 1650, which was posted with a miscalibrated score function. Players may load in their work from Puzzle 1650.
Design a protein to bind B7-2 and block autoimmune reactions! B7-2 is a signal protein in the immune system, and is important for regulating how the immune system distinguishes foreign particles from “self" cells. In some autoimmune disorders, like rheumatoid arthritis, B7-2 can activate the immune system against the body’s own self cells. We want to design a protein that binds B7-2 and blocks it from activating the immune system. Here we’ve provided the target surface of B7-2, along with a a few loop residues from a known binder of B7-2. We want to see if Foldit players can design a folded protein that contains this loop! The B7-2 surface and the binding loop are frozen in place. Good designs should form a well-folded protein that stabilizes the proline-rich binding loop. The starting structure contains 122 residues, but players may add residues at a cost of 55 points each (maximum 130 residues).
Apologies for the scoring calibration! This is a result of all of the cutpoints in the structure, which have very bad ideality.
It looks like we overcorrected for this, so solutions in this puzzle will have much higher scores than other puzzles.
Are the devs aware that scores for this puzzle are not updating properly on the Foldit website? My score is at 169546, but website shows 169338. Closing and reopening the puzzle does not help. And the problem seems to be specific to this puzzle, as other puzzles are working as they should!
I have a solution that does a better job of binding to the prolines than others. However, it scores better when mutated and losing some of those bonds. I'll share to scientists when the system is fixed, but would like to know what solution we are seeking
Thanks for the feedback! We've been having some server problems, but it's strange that only this puzzle is affected.
The puzzle expiration has been extended 24 hours, to give everyone a chance for their scores to be updated on the website.
Good question! The main goal is to design a protein that folds up with the proline-rich loop in the given shape. There could be many ways to do this, but I think good H-bonds will be key.
In particular, each proline has an oxygen atom that can make H-bonds (these backbone oxygens are not visible in the default Cartoon view options, but you can see them in Stick mode). These oxygens should either (1) make hydrogen bonds with the rest of the design, or (2) remain exposed so that they can make H-bonds with the surrounding water. If the oxygens are buried in the design and do not make hydrogen bonds, then the protein will be unlikely to fold.
Thanks for the extension. Likely you already know the scores still aren't updating properly. For example we have an evo with a much higher score in shared solutions that isn't showing on game or site scoreboards. Additionally, that solution crashed three times on load (was going to do it again to capture crash but it finally loaded.)
Have the website scoreboards updated with your high-scoring evo (currently showing 169,792)?
If you have a higher-scoring evo, can you try to share that solution with scientists?
This problem is proving very difficult for us to diagnose (if your high-scoring solutions aren't being sent to the server, we have no way of knowing about them). Your continued feedback is really helpful!
this puzzle is still not loading scores correctly
Whatever was fixed was not the prob
