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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.

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.

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.

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.

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.

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.

Design a protein with the help of the new AlphaFold prediction tool! AlphaFold is an algorithm from the company DeepMind and can predict protein structures with incredible accuracy. We want to know if Foldit players can use feedback from AlphaFold to design new proteins! After you've designed a protein, you can upload your solution to the Foldit server and get back an AlphaFold prediction about how your design will actually fold up. Players should aim for an AlphaFold confidence and similarity of 80% or more. See the blog for more details about the AlphaFold prediction tool.

This sandbox puzzle features a designed binder for the TGF receptor, created by an anonymous player in Puzzle 2014. The hydrophobic residues at the interface will make for tight binding. The polar residues at the binding interface satisfy buried polar atoms on the target, but they also ensure that the binder will fold even in the absence of the target. For more, check out Foldit Lab Report #23 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

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.

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.