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1573: HIV Protease Inhibitor Small Molecule Design: Round 3
Status: Active

Summary

Name: 1573: HIV Protease Inhibitor Small Molecule Design: Round 3
Status: Active
Created: 09/10/2018
Points: 0
Expires: 09/19/2018 - 18:00
Difficulty: Expert
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.

Categories: Small Molecule Design

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Comments

rmoretti's picture
User offline. Last seen 10 hours 59 min ago. Offline
Joined: 01/15/2010
Groups: None
Objectives

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:

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's picture
User offline. Last seen 8 hours 3 min ago. Offline
Joined: 12/27/2012
Groups: Beta Folders
problems loading 1519 solutions

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's picture
User offline. Last seen 10 hours 8 sec ago. Offline
Joined: 09/20/2010
Groups: Go Science
I'm hanging on loading 1573

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's picture
User offline. Last seen 1 day 20 hours ago. Offline
Joined: 12/07/2007
Groups: Contenders
Similar here. It crashed on

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's picture
User offline. Last seen 3 days 10 hours ago. Offline
Joined: 05/10/2008
Groups: None
hangs

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's picture
User offline. Last seen 18 hours 12 min ago. Offline
Joined: 07/26/2013
Hangs

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.

tyler0911's picture
User offline. Last seen 4 days 16 hours ago. Offline
Joined: 01/19/2011
Seconding this comment. I've

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

alcor29's picture
User offline. Last seen 12 hours 43 min ago. Offline
Joined: 11/16/2012
Hung twice

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

dbuske's picture
User offline. Last seen 13 hours 31 min ago. Offline
Joined: 09/22/2011
Groups: Beta Folders
HIV hangs

Yep, slowness and hangs for me also

dbuske's picture
User offline. Last seen 13 hours 31 min ago. Offline
Joined: 09/22/2011
Groups: Beta Folders
Fixing it!

Are you going to fix this puzzle???

toshiue's picture
User offline. Last seen 6 hours 36 min ago. Offline
Joined: 01/31/2016
Groups: Go Science
hangs continuously

hangs on every share, both machines, any client, any share. haven't been able to dl one share yet.

Joined: 02/08/2012
Groups: None
Journal of Medicinal Chemistry

This link is scholarly; Current articles on advances on drug design ligand inhibitors.

I would practice building some of these to get an idea of how to make your own. That's what I'm going to do anyway.
https://pubs.acs.org/toc/jmcmar/0/0

wisky's picture
User offline. Last seen 2 days 13 hours ago. Offline
Joined: 07/13/2011
Crashes galore

Besides crashing ever 2 minutes, this puzzle is running fine.

Joined: 09/24/2012
Groups: Go Science
See feedback

here

https://fold.it/portal/node/2005702

Hang on all track changes and/or loading shared solutions.
(Windows + Linux)

No problem with old Mac OS.

Joined: 11/18/2012
Groups: None
Multiple hangs and crashes

Multiple hangs and crashes.............fix coming soon?
(Windows)

toshiue's picture
User offline. Last seen 6 hours 36 min ago. Offline
Joined: 01/31/2016
Groups: Go Science
no shares....no evo

still can't load any shares, no evo available. this just isn't a viable puzzle. may we withdraw it until it's fixed please?

toshiue's picture
User offline. Last seen 6 hours 36 min ago. Offline
Joined: 01/31/2016
Groups: Go Science
still no evo

still refuses to load any group shares, unable to start evo on either Win7 or Win10 machine. puzzle is 2/3s over and haven't been able to start an evo yet. please withdraw this puzzle and fix it.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, RosettaCommons