Double Mutant Cycles - Quantifying Weak Interactions

4 Double Mutant Cycles - Quantifying Weak interactions 

Cockroft, S. L. and Hunter, C. A., Chemical double-mutant cycles dissecting non-covalent interactions , Chem. Soc. Rev. 2007, 36, 172-188. 

The secondary interactions must be additive functions of the mutations 

The double mutant serves as the reference state and so the individual mutations should be noninteracting. 

Each member of the cycle should have the same conformation and any structural changes must be the same on both sides of the cycle. 

---