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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!

This is a throwback puzzle to the early days of Foldit. This is another potent neurotoxin produced by scorpions, similar to that found in Puzzle 55. 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 D2 symmetric protein tetramer, with 4 identical chains of 80 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.

Design a binding pocket for the cortisol ligand! Cortisol is a natural signaling molecule that the body uses to regulate metabolism and inflammation. Commonly known as a "stress hormone," cortisol levels tend to increase under conditions of chronic stress. We'd like to design a cortisol binder that could be used to detect the hormone or sequester it from the blood stream. Cortisol is mostly hydrophobic, but has several polar atoms that need to be satisfied by H-bonds in the binding pocket!

This is a throwback puzzle to the early days of Foldit. This cow protein, found in epithelial cells of the intestine, binds calcium as it moves from the digestive tract into the blood. 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. 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 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!

Fold this Transcription factor (TF) into the electron density map! This puzzle might be tough, as this is a large protein. This electron density map comes from x-ray crystallography experiments, and outlines the shape of the folded protein, so help us determine the structure of this TF by folding it in the electron density! Sequence and additional information in the puzzle comments.

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 has no H-Bond Network Objective, but there is "Core Limit: Complex" objective meant to regulate the size of the interface between symmetric chains. An interface that is too large, with too many orange hydrophobics, can prevent the individual subunits from folding properly; on the other hand, an interface that is too small does not provide enough interactions for assembly The "Core Limit: Complex" objective will incur penalties if there are too many, or too few buried residues in the total assembly. This puzzle uses the Buried Unsats Objective, with a large penalty for buried polar atoms that can't make H-bonds. See the puzzle comments for more Objective details.

Note: This puzzle replaces the original Puzzle 2005 which used a mis-calibrated score function. Players may load in solutions from the original Puzzle 2005.