Foldit Puzzles

2023: TGF Receptor Binder Design: Round 8

Design a protein that can bind to the TGF-beta receptor! We have been seeing excellent designs from the previous puzzles, so this puzzle is set up just the same. Try to max out the Contact Surface Objective by using sidechains that pack closely against the target binding site!

2022: Revisiting Puzzle 72: Citric Acid Cycle

This is a throwback puzzle to the early days of Foldit. This short protein is a component of the α-ketoglutarate dehydrogenase complex, which is best known for its role in the citric acid cycle. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2021: Symmetric Trimer Design: H-bond Networks

Design a symmetric protein trimer, with 3 identical chains of 80 residues each! This puzzle includes a Secondary Structure Objective, so no more than 50% of your design can form helices. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.

2020: Olivetolic Acid Ligand Binder Design

Design a binding pocket for the olivetolic acid ligand! Olivetolic acid is a precursor to tetrahydrocannabinol (THC), the main psychoactive compound produced by cannabis. Scientists are interested in developing more efficient methods for THC synthesis, and a binder for this precursor could help to regulate or troubleshoot synthesis pathways. Olivetolic acid has a long hydrophobic tail that will naturally prefer to be buried in the binding pocket. But the ligand also has several polar atoms that need to be satisfied by H-bonds for successful binding!

2019: Revisiting Puzzle 71: Crystallin

This is a throwback puzzle to the early days of Foldit. This protein is found in high concentrations in the lens of the eye. Among its other functions, it is responsible for the high refractive index (and resulting optical properties) of the lens. The protein is modeled here in 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.

2018: Symmetric D2 Tetramer Design: H-bond Networks

Design a D2 symmetric protein tetramer, with 4 identical chains of 90 residues each! Unlike the cyclical C4 symmetry that we are used to, the proteins in this puzzle will come together as a "dimer of dimers" with D2 symmetry. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.

2017: IL-2R Binder Design: Round 2

Design a protein that can bind to the IL-2 receptor (IL-2R)! IL-2 is a signaling protein that helps to regulate the human immune system. When it binds to the IL-2 receptor on the surface of an immune cell, it can induce the immune cell to change its behavior or differentiate into a new cell type. The precise effects of IL-2 vary widely for different cells, depending on the cell type, the local environment, and even the concentration of IL-2. A synthetic form of IL-2 is approved in the U.S. to treat certain types of cancer, but is associated with severe side effects. We'd like to design a protein binder that can block binding at the IL-2 receptor and attenuate IL-2 signaling.

2016: Revisiting Puzzle 70: Nucleosome Protein

This is a throwback puzzle to the early days of Foldit. This protein domain is a component of the histone protein complex, which packages DNA into compact units called nucleosomes. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2015: Symmetric D2 Tetramer Design: H-bond Networks

Design a D2 symmetric protein tetramer, with 4 identical chains of 70 residues each! Unlike the cyclical C4 symmetry that we are used to, the proteins in this puzzle will come together as a "dimer of dimers" with D2 symmetry. The H-bond Network Objective encourages players to build buried, satisfied H-bond networks at the interface between symmetric chains. H-bond networks are a great way to introduce polar residues at the interface, but it's important that all of the bondable atoms make hydrogen bonds! We've also adjusted the H-bond Network Objective so that poor-scoring H-bonds may not contribute to networks; poor-scoring H-bonds will be displayed in red. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. In this puzzle, there are no limits on the Complex Core, but we've included the Complex Core objective so players can see the core residues that can be incorporated into H-bond Networks.

2014: TGF Receptor Binder Design: Round 7

Design a protein that can bind to the TGF-beta receptor! We have been seeing excellent designs from the previous puzzles, so this puzzle is set up just the same. Try to max out the Contact Surface Objective by using sidechains that pack closely against the target binding site!