Foldit Puzzles

1950: Two-sided Interface Design

Design an interface between two protein chains! In this two-sided design puzzle, you can mutate the interface residues of both chains A and B, but you may only shape the backbone of chain A. Chain A should have a substantial core to satisfy the Core Existence Objective, and it should pack tightly against chain B to satisfy the Contact Surface Objective. The goal is to create a binding interface between the two protein chains so that they will stick together in solution. However, the starting position of the two chains is important, so the locked regions 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.

1949: Revisiting Puzzle 54: Human Fyn

This is a throwback puzzle to the early days of Foldit. This kinase protein is part of a human signaling pathway that controls cell growth. 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.

1948: Designable Linker: Coronavirus Spike Binder

This is the twelfth 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 of the Month: January 2021

This sandbox puzzle features a designed protein linker for two CoV spike binders, designed by nspc in Puzzle 1927. A substantial core of orange hydrophobic residues should keep the entire protein folded into this precise shape. For more, check out Foldit Lab Report #16 on YouTube! This sandbox puzzle is non-competitive and will not award any points.

1947: 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.

1946: Revisiting Puzzle 52: Bacteria Energy

This is a throwback puzzle to the early days of Foldit. This protein is part of a metabolic pathway used by bacteria to harvest energy from sugars. 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.

1945: Designable Linker: Coronavirus Spike Binder

This is the twelfth 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.

1944: 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.

1943: Revisiting Puzzle 165: Rosetta Model 15

This is a throwback puzzle to the early days of Foldit. This protein helps to maintain the reduction potential of the cell. The starting structure is a Rosetta model. This protein contains four cysteine residues, but only two of them oxidize to form a single 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.

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.