This puzzle is a trimer, which means there are three copies of the protein. You design one copy of the protein, which appears in light yellow if you're using the default view options. The other two copies of the protein change as you design the first one. The other two copies appear in dark green.
The goal is to have all three copies of the protein stick together as if they were one unit.
If you move or rotate the first copy of the protein, the other two copies also move.
Unlike recent Foldit design puzzles, this puzzle has no filters to enforce design rules. Design puzzle filters often restrict how many segments can be in helixes, require a hydrophobic core of a certain size, and limit which amino acids can appear in certain parts of the protein.
Tools and strategiesEdit
Since this puzzle lacks filters, it's tempting to use the Cynical Helix Ploy, which involves making one or more helixes and lining things up in parallel. Helixes tend to score well in Foldit, since they have lots of hydrogen bonds and pack a lot of atoms into a relatively small space.
For this puzzle, try making two helixes with some loop segments between them.
Leave one segment of loop at each end of the protein, an "end cap" usually seen in real proteins.
Allow three segments of loop in the middle to join the two helixes.
The loop spacers would use 5 of the 40 segments. Divide the remaining segments into one helix of 17 segments, and one of 18 segments.
In schematic form, you'd have:
- Loop (1) - Helix (17) - Loop (3) - Helix (18) - Loop (1)
Unfortunately, nothing in Foldit can handle that type of schematic at the moment. (You could write a recipe to apply this schematic to a protein.)
Lacking a recipe, it's easy enough to set the secondary structure manually.
In the original interface, switch to structure mode, then right-click (or control-click) on the segment that starts a helix. Select "Assign Helix" from the wheel menu. Click on the same segment again, and drag along the backbone to "paint" the helix to the desired length.
In the selection interface, simply select the segments you want to make into a helix, then use the secondary structure icon (sheets) or the keyboard shortcut L (lowercase "l"). Then click on the helix icon or the keyboard shortcut K (lowercase "k") to make the helix.
After creating the helixes, you can use the idealize secondary structure tool to make into actual spirals.
In the original interface, right-click (or control-click) on a segment in one of the helixes, and select "Idealize SS" from the wheel menu. The helix becomes a perfect spiral. Repeat for the other helix.
In the selection interface, double-click on a segment of one helix. This selects the helix and the surrounding sections of loop. Use the idealize secondary structure icon (paint brush with tube of paint) or the keyboard shortcut 5 to create the spiral. Repeat as needed.
Once you have the two helixes, insert a cutpoint in the section of loop between them. Then use the move tool to make the helixes parallel to each other. Close the cutpoint.
Once you have the first copy of the protein ready, use the move tool again to move the three copies of the protein together. You can simply line up all three copies in parallel, or you can try aligning them at a slight angle to each other.
Once you have a starting arrangement, the next step is to mutate the protein. To get started, you can use the "mutate all" option.
In the original interface, select "Mutate" from the actions menu or use the M (lowercase "m") keyboard shortcut.
In the selection interface, de-select everything and use the mutate all icon (letter Y with an arrow and the word "all") or the Y (lowercase "y") keyboard shortcut.
Let mutate all run for a few cycles, then stop. Shake and wiggle the protein.
If the parts of the protein were too close together, they may fly apart when you wiggle. If this happens, undo (control+Z) and add bands, then wiggle again. The bands should help keep the protein together.
After shaking and wiggling a couple of times, try "mutate all" again.
These relatively simple steps should help you get a high score. Feel free to experiment with variations, such as using three helixes instead of just two.
One goal of Foldit design puzzles is to produce proteins that fold up on their own, the same way that natural proteins do.
The Foldit science evaluates player solutions in various ways. Promising solutions end up being tested in the "wet lab".
These Foldit blog posts describe the process:
So far, a designed a self-folding protein has been elusive, but recent results have been promising. Stay tuned for updates!