gitwut,
We will indeed do another sepsis puzzle once the bugs have been worked out.
It might take some time, since the issues with this particular puzzle appear to be quite severe, but I promise you that we will not give up on this puzzle.
This is a very difficult problem and we really want all of you to help us (and our collaborators at Harvard) with it, once the puzzle is posted properly.
Thank you all for your patience on this one.
In Contenders shared solutions, I've put a couple of solutions.
spv 7828 (start)
spv 7430. After rebuilding 100-104 in 7828. Wiggle All does nothing to improve this latter solution, despite the presence of backbone scores of -76 and such.
HTH
In Anthropic Dreams shares: solo3_wont_wiggle
This set of steps works as expected:
load share
wiggle at ci 1
protein moves away from sugar as expected (because of the bands to space)
disable bands while wiggling
score climbs over 7000
However, this gets stuck:
load share (or just undo your earlier wiggle)
disable bands
wiggle at ci 1
score gets stuck at 4538
At this point wiggle is stuck - you can enable the bands to space, add or remove bands, move the existing bands, change ci, shake then wiggle, run Blue Fuse, etc. but wiggle will no longer move the protein.
Expected behavior with bands enabled: bands pull protein away from sugar.
Expected with bands disabled: score climbs over 7000
What does happen: wiggle does nothing
You can drag the protein to change its score, and then wiggle will work again.
I agree with gitwut that we really need a score bonus for interactions with the ligand.
Part of the problem here might be that the loop we're working on doesn't actually want to extend in the direction of the ligand. In other words, it's not a bug in the score function, it's a physical reality that extensions of that loop away from the ligand are lower-energy than extensions of the loop that point in the direction we want. That doesn't mean it's impossible to design a loop extension that interacts with the ligand, but it does mean that we're fighting the foldit engine to do so, because all our tools are set to look for the highest score. The way to fix that problem would be a score bonus that counteracts the advantage of loops pointing in the wrong direction.
In addition to the difficulty getting the loop to stay close to the ligand, it is difficult (and costly points-wise) to keep polar sidechains next to the ligand so bonds can form. Many times I manually set hydrophilics in the spots adjacent to the sugar, but the mutate function in the scripts I was using kept replacing them with hydrophobes that scored higher because they were nicely hidden by the ligand. If the ligand is a protein, hydrophobes in the interface may make the ligand stick better, but I'm guessing that's not the case with a sugar. When you specifically want hydrogen bonds between the protein and the ligand, foldit's preference for "orange in blue out" makes it hard to keep solutions where those bonds can form. Maybe this could also be addressed with some kind of bonus; I don't know.
maybe an idea for this would be a slider like the clashImportance called bondingImportance where at this puzzle this will should get frozen to the highest (maybe also useful for other puzzles)
Thanks for this information. This has helped tracked down what I think is the cause of the problem, so hopefully we'll get a fix out soon.
In that case, let's try something radical:
Score the ligand only and ignore everything else.
We've found and fixed what is likely the cause of the wiggle lock bug. This will go out in an update shortly.
This fix has been released.