2419: Y4R: Round 4

Closed since about 2 years ago

Summary

• Created: February 16, 2024
• Expires: February 23, 2024 at 23:00 UTC
• Max points: 100

Description

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!

Top groups

• 1. Anthropic Dreams 100 pts. 15,241
• 2. Go Science 73 pts. 15,011
• 3. Contenders 52 pts. 13,970
• 4. VeFold 36 pts. 13,155
• 5. AlphaFold 24 pts. 12,491
• 6. Gargleblasters 16 pts. 12,426
• 7. Australia 10 pts. 12,075
• 8. FamilyBarmettler 6 pts. 11,644
• 9. That's a Wrap! 4 pts. 11,158
• 10. L'Alliance Francophone 2 pts. 11,034

Top soloists

• 1. gmn 100 pts. 15,241
• 2. Sandrix72 93 pts. 15,011
• 3. ucad 86 pts. 14,538
• 4. Bletchley Park 79 pts. 13,970
• 5. rosie4loop 73 pts. 13,902
• 6. LociOiling 67 pts. 13,783
• 7. nspc 62 pts. 13,630
• 8. pr0tfold 57 pts. 13,413
• 9. MicElephant 52 pts. 13,316
• 10. Dr.Sillem 47 pts. 13,155

Comments

[Sciren]

Objectives

Maximum bonus: +8000

Compound Library (max +1000)
Gives a bonus if your current compound is in the library. This uses a local cached version of the Compound Library search results to determine if the compound is in the library. If you manually create a compound that happens to be in the library (or if you load a shared solution with an on-library compound), you may need to submit the compound to the compound library search and wait to get the results back before the objective can properly recognize that the compound is in the library. (If the objective is not updating, try wiggling the structure. See this forum post for more discussion.)

Torsion Quality (max +1000)
Keeps bond rotations in a good range. Using Wiggle or Tweak Ligand can fix bad torsions. (Show highlights torsions to be rotated.)

Number of Rotatable Bonds (max +1000)
Intended to keep the ligand from getting too big and floppy. You can reduce rotatable bonds by deleting groups or forming rings. (Show highlights rotatable bonds.)

Ligand TPSA (max +1000)
Topological Polar Surface Area - Keeps the polar surface area (including buried polar surface) low. To improve, try removing oxygens and nitrogens. (Show highlights atoms contributing to higher TPSA.)

Ligand cLogP (max +1000)
A measure of polarity - Keeps the molecule from getting too hydrophobic. To improve, try adding polar oxygens and nitrogens. (Show highlights atoms contributing to higher cLogP.)

Bad Groups (max +1000)
Gives a bonus for avoiding groups that interfere with assays, which are far from the compounds in the library, or which otherwise have issues. (Show highlights groups at issue.)

Molecular Weight (max +1000)
Keeps the ligand within a reasonable size limit.

Synthetic Accessibility (max +1000)
Keeps the ligand from going too far from the compounds in the library. (Show highlights parts of the molecule at issue.)