Foldit Puzzles

Design of the Month: October 2020

This sandbox puzzle features a symmetric trimer design by Skippysk8s, from Puzzle 1888. The skew helical bundle arrangement allows for hydrophobic binding patches while keeping plenty of polar residues on all helices. For more, check out Foldit Lab Report #13 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

1908: Aflatoxin Challenge: Round 20 Loop Prediction

Refold the loops in this Aflatoxin Challenge design! In the most recent lab tests the Siegel Lab identified three well-behaved designs that show activity against aflatoxin. We want to know how these designs fold in the absence of aflatoxin. This puzzle features a protein designed by LociOiling in Puzzle 1739, but the starting structure has been partially unfolded. Help us predict the structure of this design by folding the redesigned loops!

Coronavirus Binder Metrics Sandbox

This non-competitive sandbox puzzle features a new kind of Objective that we're calling Metrics. Metrics are slow to compute, so they are calculated in the background while you're folding your protein. That means that sometimes your score will be greyed out while the metrics are computing, but if you wait just a second then they will finish and your score will regain color. See the blog for more info about Metrics in Foldit. This is a multi-start puzzle with binders for the Coronavirus spike. You can start the puzzle with (1) a fragment of the natural ACE2 receptor, (2) the designed binder LCB1, or (3) an extended chain so you can design your own. Cycle through the different starting structures by resetting the puzzle. The puzzle Objectives include three Metrics (DDG, SASA, SC), so that you can practice designing protein binders using these binder metrics. This puzzle is non-competitive and will award no points.

1907: MERS-CoV Binder Design

Design a binder for the viral spike of MERS-CoV! MERS is a respiratory disease similar to COVID-19, and is caused by a related coronavirus. There have been several MERS outbreaks since 2012, but there is still no treatment has been developed for the disease. The MERS-CoV virus is coated with a spike protein that recognizes the human protein DPP4, which is found on the surface of lung cells. A protein that binds to the MERS-CoV spike could be used as a drug to block DPP4 recognition and slow viral infection.

1906: Symmetric Trimer Design: H-bond Networks

Design a symmetric protein trimer, with 3 identical chains that assemble together! This puzzle includes a Secondary Structure Objective, so no more than 50% of your design can form helices. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.

1905: Aflatoxin Challenge: Round 19 Loop Prediction

Refold the loops in this Aflatoxin Challenge design! In the most recent lab tests the Siegel Lab identified three well-behaved designs that show activity against aflatoxin. We want to know how these designs fold in the absence of aflatoxin. This puzzle features a protein designed by Phyx in Puzzle 1739, but the starting structure has been partially unfolded. Help us predict the structure of this design by folding the redesigned loops!

1904: Coronavirus Binder Design: Round 20

Design a binder against coronavirus! This puzzle includes optional Objectives for the binder metrics. The DDG, SASA, and SC Objectives will not award any bonuses and should not affect recipes, but you can run these Objectives to check the binder metrics of your design. We've also adjusted the BUNS objective to ignore many of the "unsolvable" BUNS in the frozen target. Remember, if your designed protein creates Buried Unsats, then it will be less likely to fold and bind to the coronavirus target. (Note that this target protein includes 3 buried unsats that players may be unable to fix.) See the blog for more details about buried unsats, and for helpful tips to make a successful protein binder! Players may not load solutions from previous puzzles.

1903: Two-sided Interface Design

Note: This puzzle was closed early due to problems in the puzzle setup. A corrected version has been posted as Puzzle 1903b.

1903b: Two-sided Interface Design

Note: This puzzle replaces Puzzle 1903, which had some errors in the puzzle setup. Players may not load solutions from Puzzle 1903.

1902: Aflatoxin Challenge: Round 18 Loop Prediction

Refold the loops in this Aflatoxin Challenge design! In the most recent lab tests the Siegel Lab identified three well-behaved designs that show activity against aflatoxin. We want to know how these designs fold in the absence of aflatoxin. This puzzle features a protein designed by LociOiling in Puzzle 1739, but the starting structure has been partially unfolded. Help us predict the structure of this design by folding the redesigned loops!