Combo Conditions

Combo conditions. To solve the puzzle, fix the helix and form a hydrophobic core between the helix and the sheet.

This puzzle has two different conditions which must be satisfied.

Loci's "Combo Conditions" video

The first is a secondary structure condition, which requires a certain number of residues (or segments) be in helixes.

If you hover over the red secondary structure condition, you'll see that at least 12 residues should be in helixes.

When the puzzle starts, a number of segments are marked as helix, but their shape is not correct.

To fix the secondary structure condition, right click (or control click) on one of the helix segments and select "Ideal SS" from the wheel menu. The helix segments instantly become a perfect helix, with blue-and-white hydrogen bonds connecting every fourth segment.

The second condition requires forming a core between the helix and the sheet. Foldit usually involve a core made of mostly hydrophobic segments, amino acids which are best kept away from water.

The core condition can be difficult to meet.

As the popups suggest, click on the "show" checkbox next to the "Core Existence" condition in the conditions area. Almost all the segments in the protein are highlighted in blue, meaning they're on the outside (water side) of the protein. If you've already fixed the helix, you'll see one segment highlighted in green, meaning it's on the border between the core and the surface.

The goal is to make segments turn orange, meaning they're in the core.

If you hover over "Core Existence" in the conditions area, you'll that you need to make four segments turn orange (for a total of five) to satisfy the condition.

As a first step, try dragging the sheet toward the helix. As the sheet gets near the helix, some of the segments of helix should turn green or orange. Some of the segments of the sheet may also change color.

You can use bands between the sheet and the helix to help adjust the position. Hover over a segment, then shift-drag to draw a band to a corresponding segment on the other structure.

The shake and wiggle tools are also available. Shake can improve the score by clearing clashes between sidechains, and wiggle changes the shape of backbone, especially when there are bands. (Bands by themselves don't do anything until you wiggle.)

This puzzle can be a little touchy, but some combination of dragging and banding along with some wiggling and shaking should clear the core condition, if all else fails, reset the puzzle and try again.

When both secondary structure and the core existence conditions are satisfied at once, the puzzle completes.

Technical stuff: as you probably know by now, there are hydrophobic and hydrophilic amino acids. By default, Foldit colors the *sidechains* of hydrophobic amino acids orange, and makes hydrophilic sidechains blue. The "show" checkbox for the core existence condition on this puzzle colors the *backbone* and the sidechains to indicate whether a given segment is in the core. Segments in orange are in the core, blue means on the surface, and green is in between. So there are two different (but related) uses of orange and blue.

In real life, "hydrophobic" amino acids may appear on the surface of protein, what Foldit calls an "exposed". In general, that makes the protein less stable, meaning it doesn't score as well. But it does happen.

Likewise, "hydrophilic" amino acids may end up in the core of the protein. This is most true for the smaller sidechains like serine. Hydrophilics with long sidechains, like lysine and arginine are unlikely to end up the core, simply because they don't fit.

One strategy on this puzzle involves looking at the hydrophobic segments of the helix. Use the shift-X shortcut to highlight the exposed hydrophobics with blotchy yellow spheres. On the helix, most of the hydrophobics are on one side of the helix. Simply dragging the helix over to hide or cover these exposed hydrophobics may be enough to solve the puzzle. The yellow spheres disappear when you cover an exposed.

A successful solution to this puzzle is not necessarily a great-looking protein!

Design puzzles usually have a core existence condition. Although the condition in this puzzle can be difficult, core existence is often more difficult in a full puzzle. The only advantage in a full puzzle is that you normally have more protein to work with.

This puzzle is new as of November 2017, and doesn't have a video yet.

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