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.
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.
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.)
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.