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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.

This is a throwback puzzle to the early days of Foldit. This protein helps to regulate the human immune response, and the starting structure is a Rosetta model. The protein is modeled here in the reduced state, so no disulfides are expected to form. 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 puzzles that are still scientifically relevant.

Design a small molecule which can bind to KLHDC2! We don't want you to modify the protein, but instead use the small molecule design tools to build new small molecules which fit into the KLHDC2 binding pocket.

Design a symmetric protein trimer, with 3 identical chains of 90 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.

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.

Design a small molecule which can bind to KLHDC2! We don't want you to modify the protein, but instead use the small molecule design tools to build new small molecules which fit into the KLHDC2 binding pocket.

Design a protein that can bind to the TGF-beta receptor! 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.

This is a throwback puzzle to the early days of Foldit. This small protein, from the venom of the saw-scaled viper, interferes with the cellular adhesion machinery that allows blood clotting. This 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.

Note: This puzzle will crash if a player uses the Cut tool. The Foldit team has tracked down the bug and will release a software update shortly. In the meantime, please avoid using the Cut tool on this puzzle!

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.