Double-mutant cycles: a powerful tool for analyzing protein structure and function.

Abstract excerpt

A double-mutant cycle involves wild-type protein, two single mutants and the corresponding double mutant protein. If the change in free energy associated with a structural or functional property of the protein upon a double mutation differs from the sum of changes in free energy due to the single mutations, then the residues at the two positions are coupled. Such coupling reflects either direct or indirect...

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