Foldit Puzzles

1970: Revisiting Puzzle 59: TCR Binding Protein

This is a throwback puzzle to the early days of Foldit. This small, intracellular domain binds to the CD2 T cell receptor (TCR), and plays a critical role in T cell activation during the immune response. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1969: 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.

1964: Unsolved Huge Cryo-EM Density: Beet Virus

We are very excited about this puzzle, because our collaborators who provided us with the 4 structures from Foldit's 2019 cryo-EM paper have been unable to solve this cryo-EM structure.

1967: 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.

1966: Designable Linker: Coronavirus Spike Binder

This is the fifteenth puzzle in the designable linker series! We are providing parts of two of the best-known designed binders to the SARS-CoV-2 spike, and are challenging players to link them together with a rigid linker! One of them is LCB3 which you have seen before, but the one without any adjoining spike is called AHB2, and is another de novo protein that is meant to mimic ACE2, which is the human protein that SARS-CoV-2 binds to when it infects your cells. The two helical bundles are the parts of the two binders. They are currently connected with a flexible alanine linker that needs to be redesigned.

1965: Revisiting Puzzle 58: Insulin Mutant

This is a throwback puzzle to the early days of Foldit. These are the two chains of a bio-engineered variant of human insulin, which contains six cysteine residues that oxidize to form three disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are still scientifically relevant.

1963: Two-sided Interface Design

Design an interface between two protein chains! This puzzle starts with a fully-folded interface, but you will need to refold it in order to get credit. The Exploration Objective checks how closely your solution matches the starting structure, and any solution with RMSD < 3.0 A will not receive credit! We're hoping that Foldit players can find high-scoring variations on this starting structure. See the blog for more details.

1962: Influenza HA Binder Design: Round 3

Design a protein to bind to influenza virus! This puzzle is much like Puzzle 1956, but without the Move Limit. We've also doubled the bonus for DDG and Contact Surface Objectives, and increased the penalty for BUNS. We hope that players will be able to max out these Objectives!

1961: Revisiting Puzzle 57: Beta-Neurotoxin

This is a throwback puzzle to the early days of Foldit. This scorpion toxin is similar to the one from Puzzle 55, and binds to voltage-gated ion channels of insects. The protein contains eight cysteine residues that oxidize to form four disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1960: 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.