Foldit Puzzles

1977: 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.

1976: Influenza HA Binder Design: Round 5

Design a protein to bind to influenza virus! This puzzle is set up just like Puzzle 1968. Although there is no competition this time for the players who submit the most solutions, you are still encouraged to restart the puzzle once you reach 10,000 points. The more designs we have to test, the better our chances at finding a successful binder for influenza HA!

1975: Revisiting Puzzle 60: Beta Barrel

This is a throwback puzzle to the early days of Foldit. This protein binds fatty acids in intestinal cells. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

1974: 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.

1973: Tie2 Binder Design: Round 1

Design a protein to bind to the Tie2 receptor! Tie2 is a human protein that helps to regulate the maintenance and growth of blood vessels throughout the body. Normally, the Tie2 receptor binds a growth factor called angiopoietin, a signaling molecule that triggers the growth of new blood vessels. However, Tie2 overactivity has been implicated in several types of cancer, since rapidly-growing tumors require lots of new blood vessels to provide nutrients. We want to design a protein that could bind to Tie2 and block angiopoietin. A successful binder might be useful as a drug to modulate Tie2 activity that is necessary for tumor growth.

1972: CMG2 with Density

Fold this CMG2 protein into the electron density map! This protein is a domain of the human capillary morphogenesis protein 2 (CMG2). The CMG2 protein normally associates with other proteins in connective tissue, and is thought to be important for the formation of new blood vessels. But CMG2 is also targeted by the anthrax toxin, and has been implicated in certain types of cancer. The protein in this puzzle is a variant of CMG2 that researchers are studying to better understand its structure and function. 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 CMG2 variant by folding it in the electron density!

Design of the Month: March 2021

This sandbox puzzle features a symmetric tetramer assembly, designed by Galaxie in Puzzle 1950. This design has excellent close packing of core residues! All of the hydrophobic residues at the interface should make for tight binding, but all of the exposed hydrophobics may cause trouble for proper folding. For more, check out Foldit Lab Report #18 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

1971: Symmetric Trimer Design: H-bond Networks

Design a symmetric protein trimer, with 3 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.

1968: Influenza HA Binder Design Competition

This puzzle is part of a special binder design competition. We are challenging Foldit players to design as many proteins as possible in this special two week puzzle. When you reach 10,000 points, submit your solution for the competition using the Upload for Scientists button, and reset the puzzle to start another submission! This puzzle is much like Puzzle 1962, with a scoring offset (a score of 10,000 here is about equivalent to 17,500 in Puzzle 1962). See the blog for more details about the competition. For players that do not wish to participate in the competition, this puzzle will also function like a regular puzzle, and will award Foldit points as usual when the puzzle expires.

CD131 binder design

Design a protein to bind CD131 and reduce inflammation! The protein CD131 is a signal receptor found on the surface of immune cells, which help to control inflammation. In some patients with severe asthma, an excess of signaling molecules causes over-activation of CD131, resulting in severe inflammation that closes the airway to the lungs. We'd like to design a protein that can bind to CD131, to block signaling molecules and reduce inflammation.