Foldit Puzzles

2096: Symmetric Trimer Design with AlphaFold Predictions

Design a symmetric protein trimer, with 3 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.

2095: Revisiting Puzzle 109: Pumpkin

This is a throwback puzzle to the early days of Foldit. This is a trypsin inhibitor in pumpkins. 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. Players will NOT be able to load in any previous solutions for these puzzles.

2094: Olivetolic Acid Ligand Binder Design: Round 4

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.

2093: Symmetric Tetramer Design with AlphaFold Predictions

Design a symmetric protein tetramer, with 4 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.

2092: Revisiting Puzzle 97: Pig

This is a throwback puzzle to the early days of Foldit. This saposin protein from pig serves as an activator for lipid-desolving enzymes. This protein contains six cysteines 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 puzzles that are still scientifically relevant.

2091: VHL ligand design: Round 10

Design a small molecule which can bind VHL! This is the tenth (and final!) 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.

2090: CD47 Binder Design: Round 6

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.

2089: Revisiting Puzzle 96: Collagen

This is a throwback puzzle to the early days of Foldit. This small domain is a component of the collagen that forms the connective tissue beneath your skin! This protein contains six cysteines 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 puzzles that are still scientifically relevant.

2088: VHL ligand design: Round 9

Design a small molecule which can bind VHL! This is the ninth 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.

Design of the Month: December 2021

This sandbox puzzle features a small molecule design by an anonymous player in Puzzle 2062: VHL Ligand Design: Round 2. The central structure of this molecule has been modified with an aromatic ring system, which backs up a key hydroxyl that makes two critical H-bonds to the target protein. Keep an eye on the cLogP and TPSA Objectives to strike a balance between the hydrophobic and polar atoms in your small molecule designs! For more, check out Foldit Lab Report #27 on YouTube! This sandbox puzzle is non-competitive and will not award any points.