Residue Count (max +550 +275)
Penalizes extra residues inserted beyond the starting 152, at a cost of 55 points per residue. Players may use up to 157 residues in total.
Core Existence (max +1000)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.
Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.
SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA, SER, THR in helices.
Are we to bind with a cys bridge?
Yes, the target protein is a bit peculiar this way—a residue near the binding site makes a disulfide with a lone cysteine.
Note that the lone cysteine still has backbone polar atoms that may need to make hydrogen bonds if buried away from the surrounding water! (Try the Sticks view option and CPK coloring to see these more clearly.)
Since you mention the backbone polar atoms, should we assume that the cysteine is actually connected to something, so we should try to put part of our protein too near that point in space?
No, CYS 92 is not connected to anything except CYS 46 (by a disulfide bond).
Even though the CYS 92 backbone is not connected to other amino acids, it still has polar atoms. If these atoms are buried away from surrounding water, then your design should make H-bonds to those polar atoms.
It's not necessary for your design to interact with CYS 92. But since it is so close to the binding site, we expect that many designs will interact with it (and that's okay!).
Are we supposed to form a disulfide bond between
cys92 on the target protein and one of the residues
on our binding protein?
CYS 92 is already connected to CYS 46 by a disulfide bond, so it cannot participate in a disulfide bond with your binding protein.
Are we supposed to leave the space around cys92 empty,
or should we try to fill that space with parts of our
No, there's no need to leave empty space around CYS 92. You can fill that space with your binding protein. (But make sure to make hydrogen bonds if you bury any polar atoms!)
They are all out of our control.
Yes, we had trouble configuring the Objective to ignore those residues. We may be able to fix it in future puzzles. Sorry for the inconvenience!
Sorry, I am rather a rookie here and I don't understand one thing with this puzzle:
Does the fixed part of the puzzle consist of several peptide fragments? There seem to be gaps in the backbone.
Yes, good observation! We're using a truncated model of the target, to help with software performance.
The target protein IL6R is much larger than what is shown in this puzzle (>200 residues). We could include those other residues in Foldit, but then we would have to score and render another 150 residues, which can cause lagging tools and choppy graphics. Since those extra residues don't participate in binding, we can omit them from the puzzle without affecting the scientific validity of the challenge.
To see a more complete model of the target (and how it binds the IL6 cytokine), see the PDB entry1P9M.
Thank you very much for the explanation and the information given.
Showing the contradictions to this objective highlights areas on the IL6R. Showing the non-ideal loops (even though all were created originally with blueprint tool) shows both ends of the designed protein. The loop to nowhere.