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This sandbox puzzle features a symmetric tetramer design by ichwilldiesennamen from Puzzle 1977. An exceptional 100% satisfied H-bond network is buried at the interface with zero BUNS! That should prevent this design from forming aggregates or off-target assemblies. For more, check out Foldit Lab Report #19 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

Design a protein to bind to the Tie2 receptor! This puzzle is much like the Round 1 puzzle, except that we've increased the threshold for the Contact Surface Objective. Aim for a Contact Surface value of at least 500!

This is a throwback puzzle to the early days of Foldit. This spinach protein is critical for photosynthesis, and participates in the electron transfer chain within the chloroplast. The protein is modeled here in the 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.

Design a binding pocket for the biotin ligand! Biotin is an important vitamin, and is necessary for the regular function of many metabolic proteins. One bacterial protein called streptavidin binds to the biotin ligand extremely tightly. The biotin-streptavidin pair is well known for being one of the tightest ligand-binding interactions in all of biology. We'd like to design proteins that can bind ligands just as tightly, but this is a difficult protein design challenge. The streptavidin protein has a binding pocket that fits closely around biotin ligand and satisfies all of its buried polar atoms, and this is essential for the tight binding between the two molecules.

Design a protein that can bind to the TGF-beta receptor! TGF-beta is a human signaling molecule that cells use to communicate with one another. In some circumstances TGF-beta inhibits the immune response, and is important for regulating over-active immune cells if they risk damaging normal human tissue. However, certain types of tumors release extra TGF-beta to deceive the immune system so that the tumors can grow unchecked. We'd like to design a protein binder that can stick to the TGF-beta receptor and prevent this deceptive signaling. A successful binder could be part of a selective cancer treatment that helps the natural immune system fight tumor growth.

Fold this TNK1 protein into the electron density map! TNK1 is a non-receptor protein tyrosine kinase NRPTK that has been implicated in the regulation of cell growth and cell death. This puzzle might be difficult, as this structure is not similar to known solved proteins. This electron density map comes from x-ray crystallography experiments, and outlines the shape of the folded protein. Help us determine the structure of this TNK1 variant by folding it in the electron density!

This is the fifteenth puzzle in the designable linker series! We are providing parts of two of the best-known designed binders to the SARS-CoV-2 spike, and are challenging players to link them together with a rigid linker! One of them is LCB3 which you have seen before, but the one without any adjoining spike is called AHB2, and is another de novo protein that is meant to mimic ACE2, which is the human protein that SARS-CoV-2 binds to when it infects your cells. The two helical bundles are the parts of the two binders. They are currently connected with a flexible alanine linker that needs to be redesigned.

Design a protein to bind to the Tie2 receptor! This puzzle is much like the Round 1 puzzle, except that we've increased the threshold for the Contact Surface Objective. Aim for a Contact Surface value of at least 500!

This is a throwback puzzle to the early days of Foldit. This protein is able to absorb light and use the energy to transfer chloride ions across the cell membrane. 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 that assemble together! 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.