Closed since almost 8 years ago
IntermediateNote: Due to player reports of persistent crashing, this puzzle is now worth zero points, so players may skip this puzzle without any effect on their rankings. However, if players would like to continue playing the puzzle, we will still analyze the puzzle solutions. And of course, we appreciate all of the detailed feedback about the puzzle!
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.
See this previous blog post for more information on small molecule design, and Puzzle 1432 for the previous round. In contrast with the previous round, we're starting with a smaller starting molecule and are running without a similarity filter.
https://www.umassmed.edu/schifferlab/research/pathways-to-resistance/hiv-protease/
This link gives 9 approved inhibitors. I suggest trying to build them. Although we should probably build our own, building the already approved ones should help with making our own.
https://www.medscape.org/viewarticle/506280
This link might five more detail on the kind of protease inhibitors (PIs) to look for.
This puzzle crashes all the time for me in main (Ubuntu 16.04). No stack info: trying to reproduce.
Also frequently when trying to add an O or N I get a penalty from the Ligand cLogP filter of something absurd like 1.84467e21. Could probably get a test case on this if its not an already known problem.
everytime I goto upload a file to scientists my game crashes shortly after uploading
Windows 10 64 bit
Intermittent crashes with the following in the logfile
1: alIsAuxiliaryEffectSlot +598376 bytes (no line)
2: alIsAuxiliaryEffectSlot +598984 bytes (no line)
3: library_main +5297766 bytes (no line)
4: library_main +5297955 bytes (no line)
5: library_main +371112 bytes (no line)
6: library_main +3400005 bytes (no line)
7: library_main +3400443 bytes (no line)
8: BaseThreadInitThunk +36 bytes (no line)
9: RtlGetAppContainerNamedObjectPath +311 bytes (no line)
10: RtlGetAppContainerNamedObjectPath +263 bytes (no line)
Unfortunately, the second article requires a subscription to view.
The first article shows the three-letter codes for the protease inhibitors. The codes and the generic names are shown below. See protease inhibitor on the Foldit wiki for more.
The codes and generic names are:
2 times now, doing nothing, client maximized, latest devprev, win10 pro
1: alIsAuxiliaryEffectSlot +9025020 bytes (no line)
2: alIsAuxiliaryEffectSlot +598984 bytes (no line)
3: library_main +5297766 bytes (no line)
4: library_main +5297955 bytes (no line)
5: library_main +371112 bytes (no line)
6: library_main +3400005 bytes (no line)
7: library_main +3400443 bytes (no line)
8: BaseThreadInitThunk +36 bytes (no line)
9: RtlGetAppContainerNamedObjectPath +311 bytes (no line)
10: RtlGetAppContainerNamedObjectPath +263 bytes (no line)
My score on the board is 13562; my score on my saved/shared solution is 13577 in big type at the top.
In small type underneath my name the score is 13557.
I have also created about three times doing various things.
1519 scoring weirdness
Created should have been crashed
Found a 10th protease inhibitor on an older list, FPV (Fosamprenavir) which is rapidly metabolized into Amprenavir, hence its probably deletion from the list, but they are not chemically identical (APV = C25H35N3O6S, FPV (PDB: 3nu3) = C25H36N3O9PS). Difference may be of significance to us? (fwiw).
