Foldit Puzzles

2240: 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.

2239: Monkeypox H3 Binder Design: Round 8

Design a protein that can bind to the monkeypox H3 target! AlphaFold predictions are available for your designed binder. Once you've designed a binder for the target, upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder chain only (i.e. in the unbound state, in the absence of the target). If you load this prediction, then Foldit will attempt to align the prediction with your solution (i.e. in the bound state, making an interface with the target). If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the binder interacts with the target.

2238: cAMP Ligand Binder Design: Round 5

Design a binding pocket for the cAMP ligand! Neural Net Objective awards a 2000 pt. bonus for AlphaFold predictions with both high confidence and high similarity to the current solution. After an AlphaFold prediction is complete, load the original or predicted structure from the AlphaFold panel to receive the bonus. You can continue to work on this solution, but the bonus will disappear if the similarity drops. Note that the table in the AlphaFold panel only displays the similarity of the original solution; the true similarity of your current solution is recalculated by the Neural Net Objective as you change its structure.

2237: Electron Density Reconstruction 19

The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model. This puzzle contains four copies of the protein.

2236: 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.

2235: FMN Ligand Binder Design: Round 2

Design a binding pocket for the FMN ligand! Unlike in previous puzzles, this Neural Net Objective awards a 2000 pt. bonus for AlphaFold predictions with both high confidence and high similarity to the current solution. After an AlphaFold prediction is complete, load the original or predicted structure from the AlphaFold panel to receive the bonus. You can continue to work on this solution, but the bonus will disappear if the similarity drops. Note that the table in the AlphaFold panel only displays the similarity of the original solution; the true similarity of your current solution is recalculated by the Neural Net Objective as you change its structure.

2234: Electron Density Reconstruction 18

The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model.

2233: 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.

2232: BMPR Binder Design: Round 4

Design a protein that can bind to the BMPR target! Unlike in previous puzzles, this Neural Net Objective awards a 2000 pt. bonus for AlphaFold predictions with both high confidence and high similarity to the current solution. After an AlphaFold prediction is complete, load the original or predicted structure from the AlphaFold panel to receive the bonus. You can continue to work on this solution, but the bonus will disappear if the similarity drops. Note that the table in the AlphaFold panel only displays the similarity of the original solution; the true similarity of your current solution is recalculated by the Neural Net Objective as you change its structure.

2231: FMN Ligand Binder Design

Design a binding pocket for the FMN ligand! This puzzle enables AlphaFold predictions for your binder design, so you can upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder only (i.e. in the absence of the ligand). If you load this prediction, then Foldit will attempt to align the prediction with your solution. We are looking for designs where the raw AlphaFold prediction has a binding pocket that fits the ligand!