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This is a throwback puzzle to the early days of Foldit. This toxin, which is released by the sea anemone A. xanthogrammica, disrupts normal contraction of cardiac muscle in potential predators, and furthermore serves as a pheromone to signal danger to nearby anemones. 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 D2 symmetric protein tetramer, with 4 identical chains of 60 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. 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 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.

This is a throwback puzzle to the early days of Foldit. This toxin, produced by the Chinese cobra N. atra, induces contracture in skeletal and cardiac muscle. This protein contains eight cysteine residues 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.

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.

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 toxin, produced by the Mozambique spitting cobra, induces contracture in skeletal and cardiac muscle. This protein contains eight cysteine residues, which 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.

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.

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.

This is a throwback puzzle to the early days of Foldit. This protein, which inhibits muscle contraction in the absence of calcium ions, changes conformation in the presence of calcium to allow muscle contraction. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.