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In Foldit, "mutate" means "change to a different amino acid". In Foldit design puzzles, some segments are mutable, meaning their amino acids can be changed.

There are two distinct types of mutate. One type of mutate picks the best amino acid for one or more segments based on criteria known only to the Foldit design team. The other type of mutate changes one or more segments to a specific amino acid. The options for using these tools manually are described in mutate sidechains.

Recipes can also mutate segments.

In the Foldit Lua interface v2, the function structure.IsMutable checks to see whether a given segment is mutable. The function structure.SetAminoAcid sets a segment to a specified amino acid, but it doesn't give any indication of whether the change worked. Even for a mutable segment, some design puzzles block certain mutations. For example, mutation to cysteine may not be allowed. The function structure.GetAminoAcid can be used to compare the before-and-after values of a segment to see whether a mutation was successful.

The Lua functions structure.MutateSidechainsAll and structure.MutateSidechainsSelected attempt to mutate all or selected segments to their "best" amino acids.