Foldit Puzzles

2278: G-Protein-Coupled Receptor GPR133: Round 1

Help us take on unexplored drug targets for brain cancer! While 1/3 of all approved drugs target G-protein-coupled receptors (GPCRs), many of these receptors remain without appropriate small molecule ligands. This is a field of growing interest with many untouched possibilities for therapeutics. The receptor GPR133 used in this puzzle (also known as ADGRD1) was identified by researchers as a critical regulator of the response to hypoxia, low levels of oxygen in bodily tissue, and tumor growth in glioblastoma, a malign and very aggressive type of brain cancer. The interest in developing therapeutics is very high, and no small-molecule (ligand) is known so far. The structure of GPR133 was determined last year and the discovery of ligands would help to create novel therapeutics. Normally a larger molecule like a peptide would be used, but we would like to design a small molecule to fit inside this binding site to understand the mechanism of the receptor.

2277: Electron Density Reconstruction 31

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.

2275: Revisiting Puzzle 71: Crystallin

This is a throwback puzzle to the early days of Foldit. This protein is found in high concentrations in the lens of the eye. Among its other functions, it is responsible for the high refractive index (and resulting optical properties) of the lens. The protein is modeled here in reduced state, so no disulfides are expected to form. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2276: SARS-CoV-2 Nsp3 CACHE Challenge 3: Round 5

Compete in a challenge to design a drug targeting the SARS-CoV-2 Nsp3 macrodomain. Use the small molecule design tools and the compound library panel to find library compounds which bind to the active site of the enzyme. -- Only compounds which come from the Compound Library panel and get the Compound Library objective bonus will be experimentally tested.

2274: Electron Density Reconstruction 30

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. Some players may recall seeing this protein or a similar protein before, it's a commonly solved (and mis-solved) protein.

2272: Revisiting Puzzle 70: Nucleosome Protein

This is a throwback puzzle to the early days of Foldit. This protein domain is a component of the histone protein complex, which packages DNA into compact units called nucleosomes. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2273: SARS-CoV-2 Nsp3 CACHE Challenge 3: Round 4

Compete in a challenge to design a drug targeting the SARS-CoV-2 Nsp3 macrodomain. Use the small molecule design tools and the compound library panel to find library compounds which bind to the active site of the enzyme. -- Only compounds which come from the Compound Library panel and get the Compound Library objective bonus will be experimentally tested.

2271: Electron Density Reconstruction 29

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. This puzzle has several chains and is a bit larger than usual, so the Trim tool is recommended. The sequences are:

2270: SARS-CoV-2 Nsp3 CACHE Challenge 3: Round 3

Compete in a challenge to design a drug targeting the SARS-CoV-2 Nsp3 macrodomain. Use the small molecule design tools and the compound library panel to find library compounds which bind to the active site of the enzyme. -- Only compounds which come from the Compound Library panel and get the Compound Library objective bonus will be experimentally tested.

2269: Revisiting Puzzle 69: Scorpion Toxin

This is a throwback puzzle to the early days of Foldit. This scorpion toxin binds to voltage-gated ion channels in insects, resulting in full-body paralysis. The protein contains eight cysteine residues that oxidize to form four disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.