Foldit Puzzles

2438: 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.

2437: Y4R: Round 10

Neuropeptide Y receptor subtype 4 (Y4R) is a key player in the fight against obesity. Y4R is a type of receptor found in the body, particularly in the brain, that helps control appetite and manage energy. It's part of a larger family known as the NPY receptors, which includes four subtypes: Y1R, Y2R, Y4R, and Y5R. Y4R is especially important because it plays a big role in regulating hunger and weight. Scientists have recently discovered that Y4R is crucial for reducing appetite and helping with weight loss in both humans and mice. They've found some special molecules, called allosteric modulators, that can interact with Y4R in a unique way. Unlike typical drugs that bind directly to the main part of a receptor (called the orthosteric site), allosteric modulators attach to a different part (the allosteric site). This is like using a backdoor to influence how the receptor works. By targeting these backdoor sites, we can more precisely control the receptor's activity without interfering with other similar receptors. This means we can create safer and more specific drugs. In this puzzle, your challenge is to design small molecules that can cleverly and safely interact with Y4R's backdoor sites. These molecules could play a crucial role in creating new treatments for obesity. This puzzle is an opportunity for you to dive into the world of drug discovery and make a difference in the battle against obesity. Your creativity and problem-solving skills can help us find new ways to target Y4R and improve health!

2436: Electron Density Reconstruction 84

The structure of this protein-DNA complex has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model. You may notice that there’s a base pair in here that doesn’t look normal; it’s a Hoogsteen base pair (as opposed to Watson-Crick). Later on, we’ll ask you to play another version of this puzzle where it’s been put in as Watson-Crick instead of Hoogsteen as we’d like to see which works better. Also, a useful note from Bletchley Park for working with DNA: DNA sidechains can be turned relative to their blue arms with bands.

2435: 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.

2434: Y4R: Round 9

Neuropeptide Y receptor subtype 4 (Y4R) is a key player in the fight against obesity. Y4R is a type of receptor found in the body, particularly in the brain, that helps control appetite and manage energy. It's part of a larger family known as the NPY receptors, which includes four subtypes: Y1R, Y2R, Y4R, and Y5R. Y4R is especially important because it plays a big role in regulating hunger and weight. Scientists have recently discovered that Y4R is crucial for reducing appetite and helping with weight loss in both humans and mice. They've found some special molecules, called allosteric modulators, that can interact with Y4R in a unique way. Unlike typical drugs that bind directly to the main part of a receptor (called the orthosteric site), allosteric modulators attach to a different part (the allosteric site). This is like using a backdoor to influence how the receptor works. By targeting these backdoor sites, we can more precisely control the receptor's activity without interfering with other similar receptors. This means we can create safer and more specific drugs. In this puzzle, your challenge is to design small molecules that can cleverly and safely interact with Y4R's backdoor sites. These molecules could play a crucial role in creating new treatments for obesity. This puzzle is an opportunity for you to dive into the world of drug discovery and make a difference in the battle against obesity. Your creativity and problem-solving skills can help us find new ways to target Y4R and improve health!

2433: Electron Density Reconstruction 83

The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model. There's two different chains in this puzzle.

2432: 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.

2431: Y4R: Round 8

Neuropeptide Y receptor subtype 4 (Y4R) is a key player in the fight against obesity. Y4R is a type of receptor found in the body, particularly in the brain, that helps control appetite and manage energy. It's part of a larger family known as the NPY receptors, which includes four subtypes: Y1R, Y2R, Y4R, and Y5R. Y4R is especially important because it plays a big role in regulating hunger and weight. Scientists have recently discovered that Y4R is crucial for reducing appetite and helping with weight loss in both humans and mice. They've found some special molecules, called allosteric modulators, that can interact with Y4R in a unique way. Unlike typical drugs that bind directly to the main part of a receptor (called the orthosteric site), allosteric modulators attach to a different part (the allosteric site). This is like using a backdoor to influence how the receptor works. By targeting these backdoor sites, we can more precisely control the receptor's activity without interfering with other similar receptors. This means we can create safer and more specific drugs. In this puzzle, your challenge is to design small molecules that can cleverly and safely interact with Y4R's backdoor sites. These molecules could play a crucial role in creating new treatments for obesity. This puzzle is an opportunity for you to dive into the world of drug discovery and make a difference in the battle against obesity. Your creativity and problem-solving skills can help us find new ways to target Y4R and improve health!

2430:Electron Density Reconstruction 82

The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We'd like to see if Foldit players can use the same electron density data to reconstruct a better model. There's two chains here of the same thing, but both are missing a few residues that are slightly different.

2429: 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.