Where are the filter details? I see no comments.
Sorry! Here are the details for the filters on this puzzle:
Residue IE Score: Monitors that all PHE, TYR, and TRP residues are scoring well.
Core Existence: Ensures that at least 30% of the residues are buried in the core of your design.
Secondary Structure: Checks that no more than 50% of residues are in helices; penalties are incurred if more than 50% of residues form helices.
Secondary Structure Design: Penalizes all CYS residues. Penalizes GLY, ALA, and PRO residues in helices and sheets.
I've noticed that many of the design puzzles penalize Alanine. But I've noticed that many of the non-design puzzles, those sequences found in nature, have alanines in helices. Why the penalty?
The short answer is that alanines don't make a very stable core.
Alanine is indeed very common in natural proteins, and does favor α-helical structure. And, by default, an alanine-rich α-helix scores really well in Foldit.
However, since alanine has such a small sidechain, an alanine-rich helix has a "featureless" shape. You can imagine the sides of the helix would be relatively smooth (whereas a helix with larger sidechains would present an irregular, studded surface). If you were to design several of these helices into a bundle with an alanine-rich core, you would get a protein that forms helices in solution—and would probably even form a bundle to bury the alanines. But, the smooth sides of those alanine-rich helices would allow them to pack against each other in many different ways, effectively forming many different bundles. So instead of all the protein copies in a sample forming the same structure, you would get a wide mix of helical bundles with slightly different packing, constantly changing shape as the helices slide against one another. We say this protein exhibits molten globule behavior.
Instead, we prefer designs with bulky, interdigitated sidechains in the core. With only one way to efficiently pack those sidechains together, all the protein copies are expected to adopt a single, well-defined structure.