Foldit Wiki

Intro to Design. Two segments on the small section of protein in front can be mutated. Most of the protein is locked, and shows up in grey.

In this puzzle, the helix in front is green, except for two segments shown in orange. The orange segments have larger sidechains that are clashing with other parts of the protein.

Madde's "Intro to Design" video

Loci's "Intro to Design" video

Most of this protein is shown in grey, meaning it's locked and can't be moved.

The first step is to select Design Mode from Modes menu. Now the two orange segments can be "mutated", meaning you can change the amino acid.

Mutate wheel menu. Amino acids in the outer ring are hydrophobic, and the ones in the inner ring are hydrophilic.

In Design Mode, click on one of the orange segments. The Mutate wheel menu appears. The outer ring of the mutate wheel has the hydrophobic amino acids, and the inner ring has the hydrophilic ones.

The two problem sidechains are both pointing toward the middle of the amino acid, so it makes sense to pick a hydrophobic replacement. (Cheat: if you pick phenylalanine (F or PHE) for both segments, you're done.)

In this puzzle, only the shake tool is available, wiggle is not there. Try picking different amino acids for each of the two segments, then shake and see what happens.

One of the help bubbles for this puzzle says to "click on the Mutate Button from the menu". Unfortunately, there's no mutate button on this one. Just click on the segment you want to mutate as described above.

Technical stuff: amino acids don't mutate. The DNA that encodes the sequence of amino acids is what mutates. But close enough. The Foldit labs can always order artificial DNA to match the amino acid sequence you design. See design puzzle results for the details of what happens in the "wet lab" once a design puzzle ends.