Icon representing a puzzle

2313: KLHDC2 the Next Level: Round 2

Closed since over 2 years ago

Intermediate Overall Small Molecule Design

Summary

Created
June 09, 2023
Expires
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 2 we've expanded the allowable properties in the objectives. (Most notably, the molecule weight.) Also, in response to the difficulties people have been having finding library compounds which contain the core, we've changed the settings for the compound library. We're doing a more extensive search of the compound library databases, and then filtering for just those compounds which contain valid cores. This will mean that you're more likely to get a zero-match result from the search, but the few results you do get should be better suited to what we're looking for. We've also extended the "Core" filter to allow more related compounds (it should now permit all of the compounds which are listed with a star in the blog post).

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. Avatar for Go Science
    1. Go Science
    100 pts. 23,776
  2. Avatar for Gargleblasters 2. Gargleblasters 68 pts. 23,301
  3. Avatar for Anthropic Dreams 3. Anthropic Dreams 44 pts. 23,285
  4. Avatar for Contenders 4. Contenders 27 pts. 23,246
  5. Avatar for VeFold 5. VeFold 16 pts. 23,237
  6. Avatar for L'Alliance Francophone 6. L'Alliance Francophone 9 pts. 22,924
  7. Avatar for Ogre's lab 7. Ogre's lab 5 pts. 22,908
  8. Avatar for FamilyBarmettler 8. FamilyBarmettler 3 pts. 22,906
  9. Avatar for AlphaFold 9. AlphaFold 1 pt. 22,901
  10. Avatar for Australia 10. Australia 1 pt. 22,585
  1. Avatar for XeleX 41. XeleX Lv 1 5 pts. 22,270
  2. Avatar for lisarocca 42. lisarocca Lv 1 4 pts. 22,267
  3. Avatar for chyenutis 43. chyenutis Lv 1 4 pts. 22,265
  4. Avatar for Punzi Baker 3 44. Punzi Baker 3 Lv 1 4 pts. 22,252
  5. Avatar for EQUIPE 45. EQUIPE Lv 1 3 pts. 22,248
  6. Avatar for Alistair69 46. Alistair69 Lv 1 3 pts. 22,248
  7. Avatar for DScott 47. DScott Lv 1 3 pts. 22,248
  8. Avatar for karl07 48. karl07 Lv 1 2 pts. 22,248
  9. Avatar for Steven Pletsch 49. Steven Pletsch Lv 1 2 pts. 22,246
  10. Avatar for i tre foldettieri 50. i tre foldettieri Lv 1 2 pts. 22,245

Comments

rmoretti Staff Lv 1

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.)

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.)

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.)