We are giving you a symmetric trimer of 40 residues to design. Remember, a symmetric protein relies not only on how well folded each part is, but also on how well they interface together - and a symmetric trimer can be thought of as having three 2-fold interfaces.
There are multiple filters enabled on this puzzle that should lead you in the right direction. The ResidueIE filter ensures PHY, TYR, and TRP residues are scoring well. The "Core Exists" filter ensures the number of residues in the core is between 30% and 70%. The "Polar Core" filter that the residues in the core are properly hydrophobic. The "Layer Design" filter looks at the interactions of the residues based on the surface area of the protein. Residues can be either in the core, on the boundary or on the surface of the protein. Depending on the surroundings, the "Layer Design" filter will give you a bonus if your amino acid matches what it was expecting. Press TAB on each residue to find out more about these filters.
I think we have a bug, here. I have the "too many polar residues in the core" penalty. Every one of the highlighted sidechains is an alanine.
Correct me if I'm wrong, since it's been almost thirty years since I studied protein chemistry… but isn't alanine one of the more hydrophobic sidechains?
Wiggle doesn't happen unless you continuously start and stop the wiggle function. And even then, very soon it just stops wiggling, altogether.
Also: mutate has slowed to a crawl. It's impossible to tell if mutate has mutated all it can, or if I'm expected to wait an additional hour to see if anything actually happened.
In fact, everything on this puzzle works in slow-motion. Un-fun, practically unplayable. And no. I have a kick-butt computer, so it's not a memory or CPU issue.
We haven't been able to reproduce this issue. If you still have it, could you share a solution where this is happening with yourself and then let us know the title of the save? Thanks.
Sorry… but I restarted the puzzle and exceeded the score of the version that had a half dozen alanines, all marked as too polar for the core. I did not make any manual saves.
But I have a bigger issue with this puzzle. I will outline it, below.
Once again, a single, huge helix ends up with a much higher score than any other structure.
I designed this thing with four helices, separated by loops. Top score = 11607. Re-designed it with three helices, separated by loops. Best score = 11854.
Just for grins, I made on long, 40-residue helix with no bends in it at all. A huge cylinder. It's scored 12239, almost four hundred points above the best of my other structures.
The mega-helix loses about 200 points for an inadequate core. My multi-helix structures both get 60 bonus points for a good core.
The mega helix gets 150 bonus points for no invalid sidechains, while my multi-helix structures lose 10 or 20 points for 2 or 3 invalid sidechains.
How is it possible that a structure that violates the core requirements and could never exist in real life possibly score hundreds of points over structures that could exist?