The emerging role of insertions and deletions in protein engineering.

Most attempts to engineer the properties of proteins have employed single or multiple substitution mutations, which typically produce minor changes in structure. Recent structural and stability studies of insertion and deletion mutants clearly indicate that relatively large structural perturbations can be induced by altering the spacing of residues along the polypeptide backbone, often without major losses in protein stability. Although their effects are difficult to anticipate, insertions and deletions provide important new tools for altering protein structures in directions not achievable with substitutions alone.