2509: KCNQ1 Round 12

Closed since over 1 year ago

Summary

• Created: September 13, 2024
• Expires: September 20, 2024 at 23:00 UTC
• Max points: 100

Description

KCNQ1 is a critical gene that helps regulate the heart's rhythm by encoding the Kv7.1 potassium ion channel. Mutations in KCNQ1 can cause congenital long QT syndrome (LQTS), an inherited heart condition that increases the risk of sudden cardiac death, especially in young people. In this puzzle, your challenge is to design a new activator for KCNQ1 that can restore function in variants linked to LQTS. For this puzzle we're going to switch up the task just a little. Now we want to target the Voltage Sensing Domain (VSD) of KCNQ1. It has been found that mutations to the VSD affect how effectively a protein is transported from its site of synthesis to the plasma membrane also known as trafficking. See blog post for more details, but note that we are looking at a different target site for KCNQ1 for this puzzle.

Join us in this exciting quest to develop new treatments for LQTS and make a real difference in heart health! Your innovative designs could be the key to creating effective therapies for this serious condition.

*Note: While it may be possible to accept compounds not in the Compound Library for further testing, compounds from the CL have the highest likelihood to be selected.

Top groups

• 1. Anthropic Dreams 100 pts. 25,941
• 2. Contenders 70 pts. 24,533
• 3. VeFold 47 pts. 23,014
• 4. Go Science 30 pts. 22,774
• 5. L'Alliance Francophone 19 pts. 22,655
• 6. Marvin's bunch 11 pts. 22,561
• 7. Gargleblasters 7 pts. 22,124
• 8. Australia 4 pts. 21,772
• 9. Void Crushers 2 pts. 21,445
• 10. FamilyBarmettler 1 pt. 19,286

Top soloists

• 1. gmn 100 pts. 25,806
• 2. Galaxie 94 pts. 23,309
• 3. BootsMcGraw 87 pts. 22,946
• 4. Th1sN@me!sN0tAPun 81 pts. 22,839
• 5. bravosk8erboy 75 pts. 22,774
• 6. christioanchauvin 70 pts. 22,655
• 7. fpc 65 pts. 22,561
• 8. Bruno Kestemont 60 pts. 22,169
• 9. HuubR 56 pts. 22,124
• 10. nspc 51 pts. 22,019

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.)