Closed since about 10 years ago
Intermediate Overall DesignThis is a basic 70 residue design puzzle without any Fragment Filter. See the puzzle comments for filter details. The Baker Lab will run folding predictions on your solutions for this puzzle, and those that perform well will be synthesized in the lab. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!
100 pts.
10,333
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 at least 50% of residues are in sheets; penalties are incurred if fewer than 50% of residues form sheets.
Secondary Structure Design: Penalizes all CYS residues. Penalizes GLY, ALA, and PRO residues in helices and sheets.
Just curious…
Why does it say "More Sheets!" when it is an open design?
The secondary structure filter is what enforces more sheets:
Secondary Structure: Checks that at least 50% of residues are in sheets; penalties are incurred if fewer than 50% of residues form sheets.
I had way more then 50% residues in sheets and it still said there was not enough.
Are your sheets forming hydrogen bond "ladders" correctly?
The Secondary Structure Filter detects helices and sheets by their hydrogen bonding patterns. Simply assigning a region of your protein as "Helix" or "Loop" (e.g. using Structure Mode in Original Interface) will not affect the filter. Likewise, a single beta strand will not be counted by the filter unless it makes proper hydrogen bonds with a neighboring beta strand.
Thanks. I've got to read things more carefully.
I just noticed some odd behavior from the secondary structure and secondary structure design filters.
On one design, segment 11 is flagged by the SS Design filter. The segment is glycine, but it's intended to be a loop between two sheets. It does show a bond to segment 13, which is marked as a sheet, but I'm surprised the filter has decided it's part of a sheet.
Mutating segment 11 also has odd effects. Mutating to proline fixes 3 invalid residues in the SS Design filter, but changes the Secondary Structure filter from +500 to -300. (All I did was select segment 11 in the selection interface, then m -> p.)
Mutating segment 11 to threonine kept the secondary structure filter at +500, and fixed one invalid residue for the SS Design filter, which is what I would expect.
It seems the Secondary Structure and SS Design filters have a bit of a "hair trigger" on puzzle 1193, but perhaps it's just me. I've shared the solution in question with the scientists.
Here are the screenshots:
| [img_assist | nid=2002094 | title=1196: glycine at segment 11 | desc= | link=popup | align=left | width=640 | height=501] |
| [img_assist | nid=2002095 | title=1196: proline at segment 11 | desc= | link=popup | align=left | width=640 | height=501] |
| [img_assist | nid=2002096 | title=1196: threonine at segment 11 | desc= | link=popup | align=left | width=640 | height=501] |
Proline is unable to form a sheet bond, so putting it in a place that had a sheet bond will cause the sheet bond to disappear, even though the backbone position does not change. This loss of a bond was enough to reclassify both the proline and the residue it was previously bonded to from "sheet" to "not sheet." This would make the aas in those positions allowable under SS design, but lower your count of sheets. Putting the threonine in made the sheet bond reappear, changing both those residues back to sheet. Not sure why the glycine on the right in your pictures was reclassified though, given that its bonding apparently did not change.
A lot of people will be doing sandwiches, and a lot of people will be doing beta barrels. What structural feature causes a sheet to prefer one over the other?
