2325: KLHDC2 the Next Level: Round 6

Closed since over 2 years ago

Summary

• Created: July 07, 2023
• Expires: July 14, 2023 at 23:00 UTC
• Max points: 100

Description

Foldit players have discovered a small molecule fragment which binds well to KLHDC2. Take this starting fragment and expand upon it.

For Round 6, we've added back in the Compound Library panel, but have left off the compound library bonus. In addition, we've added flexibility to one of the pocket sidechains, and adjusted the bad group penalty to more heavily penalize carbon-carbon triple bonds.

Note: To get the most out of the small molecule design tools, we recommend changing you view settings to the Small Molecule Design Preset.

This is a project in collaboration with Boehringer Ingelheim. The structures of all compounds created as part of the collaboration puzzles as well as any experimental results from testing them will be made publicly available. All participants and game sponsors of current and future small molecule design games commit to complying with the Foldit Terms of Service including those pertaining to intellectual property.

Top groups

• 1. Go Science 100 pts. 24,548
• 2. Contenders 63 pts. 24,212
• 3. Anthropic Dreams 37 pts. 24,103
• 4. BIchallenge 21 pts. 23,875
• 5. Gargleblasters 11 pts. 23,872
• 6. Australia 5 pts. 23,602
• 7. VeFold 2 pts. 23,038
• 8. AlphaFold 1 pt. 22,960
• 9. FamilyBarmettler 1 pt. 22,495
• 10. L'Alliance Francophone 1 pt. 22,275

Top soloists

• 1. nspc 100 pts. 24,548
• 2. pr0tfold 93 pts. 24,349
• 3. Bletchley Park 85 pts. 24,212
• 4. Sandrix72 78 pts. 24,131
• 5. Bruno Kestemont 72 pts. 24,095
• 6. gmn 66 pts. 24,091
• 7. spvincent 60 pts. 24,022
• 8. LociOiling 55 pts. 23,998
• 9. Tehnologik1 50 pts. 23,879
• 10. julianfuchs 46 pts. 23,875

Comments

[rmoretti]

Objectives

Maximum bonus: +12 000

Core (max +1000)
Does the small molecule design contain the starting molecule as a substructure, or the essential features from one of the known binders?

HBond (max +1000)
Is the ligand making hydrogen bonds to the same groups on the protein as the starting structure does? (Show highlights the groups on the protein which need to be hydrogen bonded.)

Ligand Hydrophobic Interaction (max +1000)
Is the ligand making good hydrophobic packing interactions with specific residues? (Show highlights the residues on the protein which should be involved in the interaction.)

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.)

Ligand Hydrogen Bond Donors (max +1000)
Keep the number of ligand hbond donors low. (Show highlights atoms which are counted as hydrogen bond donors.)</li>

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

Element Counts (max +1000)
Gives a bonus for not having too many of particular elements. (Show highlights atoms which are over represented.)

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

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.)