2219: SARS-CoV-2 helicase CACHE Challenge: Round 6

Closed since over 3 years ago

Summary

• Created: October 28, 2022
• Expires: November 04, 2022 at 23:00 UTC
• Max points: 100

Description

Compete in a challenge to design a drug targeting the SARS-CoV-2 helicase. Use the small molecule design tools and the compound library panel to find library compounds which bind to the active site of the enzyme.

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 puzzle is part of Foldit's participation in the CACHE Challenge. From the set of all compounds submitted in the multiple rounds of puzzles, Foldit scientists will select up to 100 compounds based on the CACHE-provided criteria. Only compounds which are in a commercially available library will be selected, so it's beneficial to make use of the Compound Library panel to search for library compounds similar to your current design. But don't limit yourself to the compound library. You're more likely to get good results by alternating: optimizing the molecule with the small molecule design tools, find the closest library compound, then further refine it with the design tools.

The difference between this round and previous ones is the addition of hydrogen bond objectives to encourage formation of hydrogen bonds from the ligand to specific atom in the protein. We've also unlocked a few sidechains in the binding pocket.

Participation in CACHE puzzles is subject to the CACHE Terms of Participation, in particular “the Challenge IP [including Challenge Compounds] will be made freely available in the public domain pursuant to Creative Commons Attribution Only (CC-BY 4.0 or subsequent versions) licensing terms, with the intent that such Challenge IP may be Used and practiced by Users for any purpose”.

Top groups

• 1. Anthropic Dreams 100 pts. 19,158
• 2. Go Science 68 pts. 19,128
• 3. Foldit Staff 44 pts. 19,001
• 4. Contenders 27 pts. 18,710
• 5. Marvin's bunch 16 pts. 18,568
• 6. Gargleblasters 9 pts. 18,421
• 7. FamilyBarmettler 5 pts. 18,038
• 8. Rechenkraft.net 3 pts. 17,796
• 9. Void Crushers 1 pt. 17,574
• 10. Australia 1 pt. 17,545

Top soloists

• 51. rinze 1 pt. 17,453
• 52. AlphaFold2 1 pt. 17,442
• 53. Trajan464 1 pt. 17,406
• 54. kludbrook 1 pt. 17,400
• 55. Bletchley Park 1 pt. 17,355
• 56. blazegeek 1 pt. 17,343
• 57. Mohoernchen 1 pt. 17,338
• 58. Blipperman 1 pt. 17,338
• 59. alyssa_d_V2.0 1 pt. 17,338
• 60. Swapper242 1 pt. 17,310

Comments

[rmoretti]

Objectives

Objectives in this puzzle are driven primarily by the evaluation criteria used by CACHE.

Maximum bonus: +9 000

**2/3/4 ligand Hbonds (max +1000 between the three)
To inhibit the helicase, having hydrogen bonds to particular atoms that would otherwise be involved with RNA binding is helpful. These three objectives give bonuses for having ligand/protein hydrogen bonds to specific atoms. You'll get +500 for 2 hbonds, +800 for 3 hbonds and +1000 for 4 or more hbonds. Show highlights the protein atoms which will contribute to your bonus. Note that you can form hydrogen bonds to any 4 of the highlighted atoms to get the full bonus. (Due to technical limitations, four protein-protein hydrogen bonds are also counted in the drop-down total.)

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.)

Fraction of four-bonded carbons (max +1000)
Measures how carbons with bonds to four atoms ("sp3 hybridized") there are. Too few (too many double and triple bonded carbons) is bad. (Show highlights carbon atoms at issue.)

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.)

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.)

[BootsMcGraw]

Logging a formal complaint, here. I have FIVE hydrogen bonds to my ligand, but the game is giving me credit for only two. Why??

I don't know how to show a photo, so here's a link to it, as proof. You owe me 500 points, which is twelve ranks at the current status.

https://ibb.co/gg9QvhT

[BootsMcGraw]

Never mind… I hit the "show objective" for the atoms which count. Why are they so far away, and why can't the atoms I used count? A hydrogen bond is a hydrogen bond.

[BootsMcGraw]

Never mind either post. :-)

I now have five legitimate H-bonds, and am being credited for the max of four. Solution submitted to the scientists. Perseverance often pays off. Carry on.

[klbklb]

Hi everyone, you're going to find this silly, but I have covid, and I noticed that being in a dusty environment made me sneeze, and suddenly my nostrils were often blocked thanks to that.

Maybe dust allergens can be used to cure one of the symptoms of a stuffy nose from covid, you never know.

Spread the word you never know lol