Foldit Puzzles

2033: Revisiting Puzzle 76: Plant Seed Protein

This is a throwback puzzle to the early days of Foldit. This storage protein is used to stockpile amino acids for future use, and is found at high concentration in the seeds of certain plants. This particular protein was used by scientists in 2011 to collect the highest-resolution crystal structure to date. This protein contains six cysteine residues 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.

2032: Symmetric Trimer Design with AlphaFold Predictions

Design a symmetric protein trimer, with 3 identical chains that assemble together! 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.

2031: IL-2R Binder Design: Round 4 with AlphaFold Predictions

Design a protein that can bind to the IL-2 receptor (IL-2R)! 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.

2030: Revisiting Puzzle 75: Antifreeze Protein

This is a throwback puzzle to the early days of Foldit. This eelpout protein binds nucleated ice crystals to inhibit their growth. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2029: TGF Receptor Binder Design: Round 9 with AlphaFold Predictions

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.

2028: Revisiting Puzzle 74: Platypus Venom

This is a throwback puzzle to the early days of Foldit. This small peptide was discovered in platypus venom-a rare instance of mammalian-produced venom, although this peptide appears similar to more widespread antimicrobials. This protein contains six cysteine residues 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.

2026: IL-2R Binder Design: Round 3

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.

2025: Revisiting Puzzle 73: Polycystein

This is a throwback puzzle to the early days of Foldit. This domain is a component of a large glycoprotein in humans that has been linked to autosomal dominant polycystic kidney disease. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2024: Symmetric Trimer Design: H-bond Networks

Design a symmetric protein trimer, with 3 identical chains of 60 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.

Design of the Month: July 2021

This sandbox puzzle features a D2 symmetric design, created by an anonymous player in Puzzle 1998. The monomer subunit takes on an unusual fold that has two beta-sheets, each of which creates a distinct interface with other symmetric subunits! The monomer subunit has a lot of hydrophobic surface area, which may spell trouble for proper folding; but if it does fold and assemble correctly, we would expect extremely tight binding between subunits. For more, check out Foldit Lab Report #22 on YouTube! This sandbox puzzle is non-competitive and will not award any points.