Foldit Puzzles

1942: Designable Linker: Coronavirus Spike Binder

This is the eleventh 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.

1941: 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.

1940: Revisiting Puzzle 157: Rosetta Decoy 14

This is a throwback puzzle to the early days of Foldit. This domain is part of a T-cell receptor that recognizes pathogens in the body; the starting structure is a Rosetta model. This protein contains two cysteine residues which oxidize 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.

1939: Designable Linker: Coronavirus Spike Binder

This is the tenth 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.

1938: 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.

1937: Revisiting Puzzle 153: Rosetta Decoy 13

This is a throwback puzzle to the early days of Foldit. This pilin protein allows the P. aeruginosa bacterium to adhere to human cells, sometimes resulting in infection. The starting structure is a Rosetta model. This protein contains two cysteine residues which oxidize 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 puzzles that are still scientifically relevant.

1936: Designable Linker: Coronavirus Spike Binder

This is the ninth 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.

Snowflake Holiday Sandbox

Design your best-looking snowflake! Take a break with this non-competitive, non-scientific puzzle and fold up a protein chain with 6-fold symmetry. This puzzle is not worth any points, and no solutions will be analyzed for scientific merit. But the Foldit team will sort through any solutions that you share with scientists, and we'll pick out our favorite snowflake designs to be highlighted in the next newsletter!

1935: Two-Sided Interface Design

Design an interface between two protein chains! This puzzle is much like Puzzle 1929, with a suite of Core Existence Objectives to ensure that both chains have a substantial core. 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.

Design of the Month: December 2020

This sandbox puzzle features a designed protein linker for two CoV spike binders, by Jumper2, Mike Lewis, and Enzyme, from Puzzle 1912b. The designed linker region makes lots of contacts with both of the regions that it connects. More buried hydrophobics would make this linker even more rigid! For more, check out Foldit Lab Report #15 on YouTube! This sandbox puzzle is non-competitive and will not award any points.