I wanted to comment on the mutate function in relation to the Marburg puzzles (but really this applies to all design puzzles). Vmulligan commented that some sheets have an edge strand that does not contribute to the hydrophobic core. I think this is caused by the mutate function, which commonly puts blue sidechains on both the inner and outer surfaces of edge strands. Most people run scripts that use the mutate function repeatedly on design puzzles, and if the blue AAs score even a tiny bit better they are kept by the script. Once the blue sidechains are in place, wiggle will tend to turn them (sidechain and backbone both) further away from the core and toward the water, where if they were orange wiggle would keep them turned more inward.
The only way I kept my 1108 sheets orange on one side (given that they were all edge strands) was by setting them to orange manually and not allowing any scripts to use the mutate function from then on. Players may not realize there is a reason to disallow mutate in the scripts, or they may be unwilling to forego the points that mutate brings. Even after using mutate scripts, they could manually switch those inner surface AAs to orange, do a shake and wiggle, and share that version with scientists, although the backbone would have been optimized for the blue AAs. I suspect the scientists could use Rosetta to substitute hydrophobes on those edge strands and re-optimize if the solution is otherwise promising.
Maybe the core existence filter could give some points for having a large enough number of sidechains in the core, and additional points for those sidechains actually being orange. Then the scripts would prefer the orange ones in those edge positions where they are in contact with the core on one side and water on the other side.
Another problem with the mutate function is that it will put a glycine anywhere there is an unusual backbone angle. Once the glycine is there, the wiggle function has no motivation to make that residue have a more normal backbone angle. I prefer to manually change almost all glycines to something else and require the subsequent rebuilds and wiggles to find a backbone position that the more rigid AA can take, but again I have to not let mutate run in any scripts after that or the glycine is likely to come back. The fragment filter rejects the backbone if it is too unnatural, but wiggle doesn't "know" about that, so you have to luck into a good rebuild before the fragment will be fixed, and if the glycine stays there is no guarantee it will stay fixed.
Mutate also puts glycine anywhere there is no room for a sidechain, and again once the glycine is there, there is no motivation for wiggle or for rebuild scripts to make more room, and the glycine just gets more entrenched as the scripts optimize things around it. Glycines make designed proteins floppy and less likely to fold up as predicted, so I hate getting stuck with them.
In short, if you want to build solutions that meet the scientists' requirements, the Mutate function may be working against you, and after the early game you may be better off without it. Fix your hydrophobes and glycines by hand, maybe add in a couple of prolines for stiffness, and let your non-mutating scripts make them work.