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1573: HIV Protease Inhibitor Small Molecule Design: Round 3

Closed since over 7 years ago

Small Molecule Design

Summary

Created
September 10, 2018
Expires
Max points
100
Description

Due to reports of persistent crashing and issues with loading/saving solutions, we've changed this puzzle to be worth zero points. We're leaving it open, though, for those people who still want to play around with it.

The goal of this puzzle is to change the chemical structure of the ligand in the center of the protein to find better inhibitors of HIV protease. It's less about changing the protein to fit the ligand, and more about changing the ligand to fit the protein. Use the Ligand Design tool in the selection interface (or the "Ligand Design" mode in the original interface) to alter the chemical identity of the inhibitor.

The big change on this puzzle versus the previous rounds is how we are scoring the small molecules. We looked at all the interesting designs from previous rounds, and altered scoring (primarily via objectives) to encourage more drug-like small molecules.

See the previous blog post for more information on small molecule design, and Puzzle 1432 and 1519 for the previous rounds. You should be able to load structures from round 2 (puzzle 1519) into this puzzle.

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Comments

rmoretti Staff Lv 1

Molecular Weight (max 2000 pts): Penalizes larger (over 630 Da) small molecules.

Number of Rotatable Bonds (max 1000 pts): Penalizes very flexible small molecules. (Click "Show" to highlight rotatable bonds.) Bonds in rings don't count as "rotatable".

Ligand Substructures (max 1000 pts): Penalizes substructures which either occur rarely in drug like molecules, or were over-represented in previous rounds:

  • Peroxides
  • Nitro and nitroso groups
  • Thiols
  • Quaternary amines
  • Amidines </ul> Synthetic Accessibility (max 1000 pts): Penalizes compounds which are harder to make. (Click "Show" to show troublesome areas of the molecule.) Ligand Hydrogen Bond Acceptors (max 1000 pts): Penalizes compounds with too many (14 or more) hydrogen bond acceptors. Ligand Hydrogen Bond Donors (max 1000 pts): Penalizes compounds with too many (7 or more) hydrogen bond donors. Ligand cLogP (max 1000 pts): Penalizes compounds which are too hydrophobic.

LociOiling Lv 1

I was able to load one puzzle 1519 solution.

After saving the solution for puzzle 1573, the client hung during the upload.

Another client could see the share for 1573, but hung trying to download it.

After restarting the second client, the downloaded solution appeared twice, but the client hung trying to upload it.

Back on the first client, trying to open a different, locally-saved solution for 1519 resulted in a hang.

Working on a feedback, just an early warning….

pauldunn Lv 1

I'm hanging on loading 1573 tracks.

I've hung when doing some operation. When I get back into foldit and try to go to that track, it hangs.

spvincent Lv 1

Similar here. It crashed on me and subsequent attempts to play the puzzle also result in a crash on opening.

Main/Ubuntu 18.04

Hanto Lv 1

hangs terribly on download, managed to mae one create a valid save point, cannot download solution to other clients, all fresh clients, just opened

robgee Lv 1

Interesting, i got my score on the table then it crashed. Now the interesting thing is when an operation is approaching my registered score it crashes. I have tried umpteen times and whenever i get near that scoreboard score it crashes, whether i be shaking, wiggling or wiggling sidechains.
Oh Yeah, i couldnt get any recipes to run at all, instant hang.

alcor29 Lv 1

Win10/64; Main, Original UI. Tried to load atom and hung. Second attempt tried wiggle and it hung. Not playable as is.

tyler0911 Lv 1

Seconding this comment. I've probably experienced 20 hangs in the midst of shakes and wiggles, all of which took place within 10 points of my current best score. Unplayable for me in its current state