Foldit Puzzles

Design of the Month: December 2022

This sandbox puzzle features a BMPR binder design by nspc from Puzzle 2226. The target is extremely polar, and this design makes excellent H-bonds at the binding site. But we may need more hydrophobic contacts to make a tight binder! For more, check out the latest

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!

2230: Revisiting Puzzle 55: Scorpion Toxin

This is a throwback puzzle to the early days of Foldit. This scorpion toxin binds to voltage-gated ion channels in insects, resulting in full-body paralysis. 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 and to provide newer players with problems that are still scientifically relevant.

Design of the Month: November 2022

This sandbox puzzle features a cAMP ligand binder design by ichwilldiesennamen from Puzzle 2211. This protein design does a great job of making H-bonds to satisfy buried polar atoms on the cAMP ligand target. For more, check out the latest Foldit Lab Report on YouTube! This sandbox puzzle is non-competitive and will not award any points.

2229: Monkeypox H3 Binder Design: Round 7

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.

2228: cAMP Ligand Binder Design: Round 4

Design a binding pocket for the cAMP 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!

2227: Electron Density Reconstruction 17

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.