Foldit Puzzles

1934: Revisiting Puzzle 150: Rosetta Decoy 12

This is a throwback puzzle to the early days of Foldit. This human protein helps to regulate the reduction potential of the cell, and should be modeled here in reduced form (without disulfides bonds). We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are still scientifically relevant.

1933: Designable Linker Puzzle: Coronavirus Spike Binder

This is the eighth 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! 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.

1932: Symmetric Tetramer Design: H-bond Networks

Design a symmetric protein tetramer, with 4 identical chains that assemble together! 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.

1931: Revisiting Puzzle 148: Rosetta Decoy 11

This is a throwback puzzle to the early days of Foldit. This small protein is a component of the major histocompatibility complex (MHC) which is essential to a functioning immune system. The starting structure is a Rosetta model. This protein contains two cysteine residues that are oxidized to form one disulfide bond. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are still scientifically relevant.

1930: Designable Linker Puzzle: Coronavirus Spike Binder

This is the seventh 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! 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.

1929: Two-sided Interface Design

Design an interface between two protein chains! This is a followup puzzle to Puzzle 1903b, with a greater allowance of insertable residues and a stricter Core Existence Objective. The starting structure includes two helical hairpins that are frozen in place and separated from one another. We want to build on these hairpins to create a binding interface between the two protein chains. However, the starting position of the hairpins is important, so the locked hairpins are held in place by strong constraints. The only way to make the two chains bind will be to fold up a brand new interface between them.

1928: Revisiting Puzzle 147: Rosetta Decoy 10

This is a throwback puzzle to the early days of Foldit. This protein is part of a signaling pathway that regulates sporulation in B. subtilis; the starting structure is a model produced by Rosetta. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with puzzles that are still scientifically relevant.

1927: Designable Linker Puzzle: Coronavirus Spike Binder

This is the sixth 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! 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. Note that this puzzle has as different starting structure than previous puzzles and is about linking a different pair of the same binders.

1926: MERS-CoV Binder Design: Round 7

Design a binder for the viral spike of MERS-CoV! We really liked some of the top-scoring solutions coming out of the previous Round 6 puzzle, and this puzzle is set up the same way. In this puzzle, the Metrics have a ramped bonus; as you improve DDG, SASA, and SC, you will get an increasing bonus until you reach the threshold of DDG < -40, SASA > 1500, and SC > 0.6, and then the bonus will be capped. Remember that Metrics are slow to compute and run in the background, so gameplay may be different from regular puzzles. See the blog for more info about Foldit Metrics.

1925: Revisiting Puzzle 146: Rosetta Decoy 9

This is a throwback puzzle to the early days of Foldit. This protein is a phosphatase that participates in several metabolic pathways; the starting structure is a model produced by Rosetta. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are scientifically relevant.