1595: Aflatoxin Challenge: Round 12

Summary

Name:

Status:

Closed

Created:

11/02/2018

Points:

Expired:

11/09/2018 - 23:00

Difficulty:

Intermediate

Description:

Note: Due to a bug in solution sharing and loading, this puzzle is worth zero points and will close early. We encourage players to play replacement puzzle Puzzle 1597 instead, although we will still analyze the solutions from this puzzle if players wish to keep working on their designs. Unfortunately players may not load solutions from this puzzle into the replacement Puzzle 1597.

Redesign the active site to bind aflatoxin! This is Round 12 of the Aflatoxin Challenge. This puzzle is much like the previous round, with some active site mutations from the Siegel Lab, and players may load solutions from Round 11 into this puzzle. However, players have some more freedom in this puzzle to redesign three loops around the active site where aflatoxin binds. Players may insert up to 20 extra residues into these designable loops, at a cost of 20 points per residue. Parts of the scaffold protein have been trimmed to reduce the size of the puzzle, and we've upweighted ligand interactions by a factor of five. We'd like to see if Foldit players can design proteins that make more interactions with the ligand! See the blog for more details.

Aflatoxins are a class of poisonous compounds that contaminate a significant portion of the global food supply. In this puzzle, players are challenged to redesign an enzyme that could break down aflatoxin molecules. The majority of the protein is frozen, with the aflatoxin ligand fixed in a binding pocket. Surrounding the binding pocket are a number of loops that might be redesigned without affecting the folding stability of the protein. In these loops, players may manipulate the protein backbone and mutate the residue sidechains. Redesign the loops of this protein to better bind the aflatoxin ligand!

This is the twelfth puzzle of our Aflatoxin Challenge, sponsored by Mars Inc. and Thermo Fisher Scientific. Promising designs will be tested by the Siegel Lab at UC Davis. By participating in the challenge/game, the players agree that all player designs will be available permanently in the public domain, and the players will not seek intellectual property protection over the designs created as part of the challenge/game.

Categories:

Rank

Group

Score

Points

13,282

13,145

13,141

13,119

13,085

Rank

Player

Group

Score

Points

13,145

13,122

13,115

13,093

13,085

Rank

Player

Group

Score

Points

13,282

13,141

13,131

13,119

13,081

Sun, 11/04/2018 - 23:41

NinjaGreg 31 13

Offline

Joined: 05/21/2010

Groups: Go Science

Appreciate the new puzzle, but ...

... the fixed part of the protein isn't fixed. The part between the loops we could modify before, and the new one we could modify (the one fastened at both ends), came loose when I was pulling on the latter loop. Probably not what you intended.

Sun, 11/04/2018 - 23:42

NinjaGreg 31 13

Offline

Joined: 05/21/2010

Groups: Go Science

Segs 46-65

Guess I could have determined that before posting the prior comment.

Tue, 11/06/2018 - 20:03

bkoep 88 753

Offline

Joined: 11/15/2012

Groups: None

Shared solution?

Hm, I'm having trouble reproducing this. Can you share your solution with scientists?

The three designable loops are not locked in place at all. You should have complete freedom to move them around and even separate them from the protein (but the should score poorly if you extend the cutpoints).

However, that range of residues (46-65) should be completely fixed. (Note that, if any residues have been inserted into your solution then the numbering will be off. It will be easier for us to debug the shared solutions.)

Wed, 11/07/2018 - 11:36

Mark- 39 8

Offline

Joined: 08/05/2009

Groups: Contenders

Shared solutions

I can get my 44-63 residues to move by idealizing residues 27-43. They appear to return from where they came from but have uploaded my current solution for someone to check out as I did make a nice score gain around that time.

Uploaded two solutions one is my current high score and the other is after idealizing res. 27-43.

Happy to answer any further questions

Wed, 11/07/2018 - 21:26

bkoep 88 753

Offline

Joined: 11/15/2012

Groups: None

Replacement puzzle

Thanks for the feedback, all! It seems that some of these problems (see here) were related to solution sharing. When you encountered this bug, were you working with a solution that was shared from the previous aflatoxin round (Puzzle 1590b)?

We've closed this puzzle and reposted it with sharing disabled, as Puzzle 1597: Aflatoxin Challenge: Round 12b. If you continue to encounter these problems in the new puzzle, please let us know!