Since the first Immunotherapy Design Puzzle (539) gave really interesting results, we start off with a new one in this series. The goal is again to find a solution which binds the CTLA-4 protein (more background here: http://fold.it/portal/node/992285), however you are now targeting the native binding site of the CTLA-4 protein. Nature already came up with a beta-sheet which is capable of binding this region, we are now searching for a helix to interact with the site.
and please check out the blogpost about this: http://fold.it/portal/node/992498
In a future iteration, can we have slightly weaker constraints on the binding site? I'd like to work in the area around 91, which is just far enough away that the constraint makes it difficult, but I think you could get good interactions there.
It is indeed an interesting area with the hydrophobic over there, but since Ile91 is relatively far away from the natural binding site, it is constrained in this puzzle.
Ah, thanks. I was thinking maybe it would still be close enough to interfere with the natural binding site, maybe depending on the backbone behind the helix.