Foldit Puzzles

2287: G-Protein-Coupled Receptor GPR133: Round 4

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.

2286: Electron Density Reconstruction 34

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.

2285: Revisiting Puzzle 74: Platypus Venom

This is a throwback puzzle to the early days of Foldit. This small peptide was discovered in platypus venom-a rare instance of mammalian-produced venom, although this peptide appears similar to more widespread antimicrobials. This protein contains six cysteine residues that oxidize to form three disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

2284: G-Protein-Coupled Receptor GPR133: Round 3

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.

2282: Electron Density Reconstruction 33

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 three copies of the same protein here, but not all the segments are visible. It's pretty big, so this is one where the Trim tool might come in handy. One other note: if you happen to glance at the PDB entry; you might recognize the names of some of the authors for their involvement in Foldit. Not everything is perfect the first time around...

2283: Revisiting Puzzle 73: Polycystein

This is a throwback puzzle to the early days of Foldit. This domain is a component of a large glycoprotein in humans that has been linked to autosomal dominant polycystic kidney disease. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.

Design of the Month: March 2023

This sandbox puzzle features a Monkeypox H3 binder design by LociOiling from Puzzle 2259. This binder has a huge hydrophobic interface and excellent Objective scores, so we think it could bind tightly to the target. For more, check out the latest Foldit Lab Report on YouTube! This sandbox puzzle is non-competitive and will not award any points.

2281: G-Protein-Coupled Receptor GPR133: Round 2

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.

2279: Electron Density Reconstruction 32

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.

2280: Revisiting Puzzle 72: Citric Acid Cycle

This is a throwback puzzle to the early days of Foldit. This short protein is a component of the α-ketoglutarate dehydrogenase complex, which is best known for its role in the citric acid cycle. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been.