Foldit Puzzles

2087: TGF Receptor Binder Design: Round 14

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

2086: Revisiting Puzzle 95: Chicken

This is a throwback puzzle to the early days of Foldit. Signals from the nervous system induce Ca²⁺ release within muscle cells. This muscle protein, which normally inhibits muscle contraction, changes shape in the presence of Ca²⁺ to allow muscle contraction. 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.

2085: VHL ligand design: Round 8

Design a small molecule which can bind VHL! This is the eighth in a series of puzzles using the small molecule design tools to design small molecule binders to the von Hippel-Lindau E3 ubiquitin ligase. We don't want you to modify the protein, but instead we'd like you to build new small molecules which fit into the VHL pocket. See the new "Inside the Pocket" and "Fun with Fragments!" tutorials to learn how to use the small molecule design tools.

2084: Symmetric Tetramer Design with AlphaFold Predictions

Design a symmetric protein tetramer, with 4 identical chains of 70 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.

2083: Revisiting Puzzle 94: Mouse

This is a throwback puzzle to the early days of Foldit. This protein recruits components of the immune system, and normally keeps white blood cells concentrated in the lymph nodes. However, it also plays a part in the inflammatory response, when immune cells are required to fight an infection. This protein contains four cysteines that oxidize to form two 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 easier puzzles that are still scientifically relevant.

2082: VHL ligand design: Round 7

Design a small molecule which can bind VHL! This is the seventh in a series of puzzles using the small molecule design tools to design small molecule binders to the von Hippel-Lindau E3 ubiquitin ligase. We don't want you to modify the protein, but instead we'd like you to build new small molecules which fit into the VHL pocket. See the new "Inside the Pocket" and "Fun with Fragments!" tutorials to learn how to use the small molecule design tools.

2081: Olivetolic Acid Ligand Binder Design: Round 3

Design a binding pocket for the olivetolic acid 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. If you continue working off of the AlphaFold prediction, you may need to make adjustments in the binding pocket where the ligand makes contact with your binder design.

2080: Revisiting Puzzle 93: Spider Toxin

This is a throwback puzzle to the early days of Foldit. This small toxin is produced from the funnel-web spider A. aperta, and induces paralysis in insects by blocking calcium channels. This protein contains eight cysteines 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 easier puzzles that are still scientifically relevant.

2079: VHL ligand design: Round 6

Design a small molecule which can bind VHL! This is the sixth in a series of puzzles using the small molecule design tools to design small molecule binders to the von Hippel-Lindau E3 ubiquitin ligase. We don't want you to modify the protein, but instead we'd like you to build new small molecules which fit into the VHL pocket. See the new "Inside the Pocket" and "Fun with Fragments!" tutorials to learn how to use the small molecule design tools.

2078: CD47 Binder Design: Round 5

Design a protein that can bind to CD47! 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.