New Foldon Symmetry puzzles

Started by beta_helix

beta_helix Staff Lv 1

Foldon is a small, 27 residue domain from the C-terminus of a phage virus protein called fibritin. It functions to ensure trimerization and proper folding of the rest of the fibritin domain, but it folds just as capably in isolation. Biophysicists have taken note of its remarkable stability and propensity for trimerization, and have successfully fused foldon to other domains, forming a number of engineered trimeric proteins.

Your job, in this puzzle, is to take an opposite approach. Instead of attaching three copies of a known domain to foldon in order to form a trimer, you’ll be given twenty extra residues extending from foldon’s
N-terminus and asked to fold these chains into a larger trimeric domain that includes foldon. You’ll be allowed to move foldon around as well, but you can only mutate the residues in the polyalanine extension. And remember, three-fold symmetry will be enforced!

Our hope is to synthesize one of your best-scoring structures, in an attempt to generate (via NMR or X-ray crystallography) an experimental structure!

We’ll be using foldon, and some of the larger trimer domains that you generate, in our efforts to make higher-order assemblies: rigid crystals, capsules, and nanowires.

DrLemming Lv 1

Good Question! I helped put the puzzle up, so I'll field it:
We'd considered locking the main "normal" part, but thought it might be a little too restrictive. Players might build new interactions between the new chains and the normal part. We want the normal part to be flexible enough to jiggle a bit and optimize those potential interactions. Foldon is robust enough that it should stay mostly as-is unless it's pulled on, but you can always make judicious use of the "freeze" function if you're worried. :) And if something even lower-energy can be designed with those residues… well, it could be an interesting surprise. Interesting could be good.

But if we do see a lot of low energy stuff with "broken" or highly aberrant Foldons - stuff that doesn't look like it should be low energy - we'll know to freeze "normal" parts for future related design puzzles.

Thanks for the question, and happy protein building! :D