Foldit Puzzles

1986: Biotin Ligand Binder Design

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 of the Month: April 2021

This sandbox puzzle features three solutions submitted by LociOiling for our Influenza HA Binder Design Competition. Reset the puzzle to cycle through the three different designs. All of these designed binders look like they have a good chance of folding correctly, and orange hydrophobic residues at the target interface will make for tight binding. Look out for blue polar sidechains on the target that are buried by the binder; if the binder does not make H-bonds with the polar atoms on these sidechains, they will become unstable BUNS and prevent binding! For more, check out Foldit Lab Report #19 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

1985: TGF Receptor Binder Design: Round 2

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.

1984: TNK1 with Density

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!

1983: Designable Linker: Coronavirus Spike Binder

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.

1982: Tie2 Binder Design: Round 2

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!

1981: Revisiting Puzzle 62: Halorhodopsin

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.

1980: Symmetric Tetramer Design: H-bond Networks

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.

1979: TGF Receptor Binder Design: Round 1

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.

1978: Revisiting Puzzle 61: Designer Protein Top7

This is a throwback puzzle to the early days of Foldit. This protein was designed by the Baker Lab in 2003, and has a topology unlike any natural protein yet discovered. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.