Foldit Puzzles

2184: Symmetric Hexamer Design with AlphaFold Predictions

Design a symmetric protein hexamer, with 6 identical chains of 80 residues each! This puzzle enables AlphaFold predictions for the monomer subunit of your design, so you can upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your monomer subunit only (i.e. in the unbound state, in the absence of other symmetric copies). If you load this prediction, then Foldit will attempt to align the prediction with your solution. If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the monomer subunit interacts with symmetric copies.

2183: CD22 Binder Design: Round 8

Design a protein that can bind to CD22! This puzzle has a reduced BUNS penalty so that players can focus on other Objectives--but don't forget about BUNS completely! This puzzle enables AlphaFold predictions 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.

2182: Revisiting Puzzle 144: Rosetta Decoy 8

This is a throwback puzzle to the early days of Foldit. The function of this thermophilic protein is unknown, but it is unusual among intracellular proteins in that the native structure includes disulfide bonds. This protein contains six cysteine residues that are oxidized 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.

2181: Two-sided Strand Binder Design: Round 2

Design a beta strand and a separate protein that can bind to it! This puzzle is similar to the previous Round 1 puzzle, except for a new Secondary Structure Objective that will penalize designs with >50% helices. We think it will be important to design a binder that forms a strong beta sheet around the target strand.

2180: Symmetric Terbium Binder Design

Design a symmetric trimer around a terbium binding site! Terbium is an element in the lanthanide series of the periodic table. Because of their unique magnetic properties, lanthanides like terbium are useful for MRI medical imaging. We'd like to design a protein that can bind lanthanide ions for enhanced MRI imaging. Terbium can be be bound with 3-fold symmetry, so a protein trimer could be the perfect binder!

2179: Electron Density Reconstruction 11

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. In addition to the protein chain, puzzle includes a glutathione ligand that is fixed in place.

2178: CD47 Binder Design: Round 11

Design a protein that can bind to CD47! This puzzle has a reduced BUNS penalty so that players can focus on other Objectives--but don't forget about BUNS completely! 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.

Design of the Month: July 2022

This sandbox puzzle features a symmetric tetramer design by spvincent in Puzzle 2159. AlphaFold predicts the monomer unit will fold with high confidence, and an H-bond network at the interface should help to prevent off-target assemblies. For more, check out Foldit Lab Report #34 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

2177: Two-sided Strand Binder Design

Design a beta strand and a separate protein that can bind to it! This is a two-sided design problem, where we can design the sequence of both binding partners. The goal is to design a pair of proteins that will self-associate in solution. This is especially useful for bioengineering applications where we might want to use a short peptide as a "signal" that can be recognized by its binding partner. Although the short peptide may be flexible in solution, we would like to bind it in the shape of beta strand, so the target backbone has been frozen as a beta strand. However, you may still change the sidechains of the strand target to any amino acid you want!

2176: Revisiting Puzzle 143: Rosetta Decoy 7

This is a throwback puzzle to the early days of Foldit. This enzyme helps to regenerate a cofactor that is necessary for nucleic acid synthesis; the starting structure is a model produced by Rosetta. This protein contains only one cysteine, so no disulfide bonds are expected. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.