As some of you may have noticed (http://fold.it/portal/node/989140), we unveiled a new wrinkle in this most recent puzzle: we added implicit rubber bands to position a tryptophan residue in a pocket on the opposite protein interaction partner. You will see these sorts of problems in the months ahead.
The reason we are posting these sorts of puzzles is to help us better design proteins that can inhibit the flu virus. In many cases, we can identify an interaction between a disembodied amino acid and protein surface that is likely to be very beneficial. The trick is to identify a backbone configuration that can harbor that sidechain.
It turns out that we can do this for simple cases where the backbone is a helix or a sheet; but where the backbone is a loop, we are so far unsuccessful at sampling the correct configuration to allow design of new binders. But this is one of the most important classes of problems in protein-protein interactions! For example, many structures of human antibodies bound to proteins of pathogenic organisms fall into this class.
We are relying on you Foldit players to teach us the sorts of strategies we should be attempting for these challenging but very rewarding problems!
I very much enjoy the challenge presented by the FoldIt problems. However, from a pure research standpoint it may be interesting for us folders to have a little extra leeway during the next interface design puzzle.
While you can keep the same format you have now, it may be interesting to see what can happen if we are allowed to grow or shrink the loop to achieve a better pocket fit.
Also, while it is useful in a puzzle like this to have a given point of contact (the tryptophan you banded in for us) an open model may also give interesting results.
So here's my suggestion: for the next interface puzzle, offer two variations of the same puzzle. The first can be just like this one with the fixed length loop and the pre-formed bands. The second would not have the bands and would allow adding/removing elements from the loop we are allowed to manipulate.
The problem we have noticed about letting players add/remove residues is that everyone always adds the maximum possible number of amino acids. The reason for this is simple: Rosetta gives you a better score if you have more residues.
The new puzzle we just posted, 393: Design the Interface 7: http://fold.it/portal/node/989145
needs work at the terminal end of the protein, so we are able to give you a lot more leeway compared to the previous Design the Interface puzzles.
Despite all the restrictions we had given you, however, we still noticed quite a lot of variation in all the player solutions!
Is it possible to make any added amino acids neutral with regards to score? It seems like the best strategy is to subtract a base amount for each amino added.
