∆G AB-L is the binding free energy between ligand and protein complex AB. The last line of Eq. indicates that ∆G φ quantifies the non-additive part in addition to pairwise binding free energies. Rearranging Eq. ( ) with the thermodynamic cycle depicted in Figure , ∆G φ can be decomposed into contributions from geometry (∆G s φ,geo ), cooperative solvation (∆G s φ,solv ), and gas-phase cooperativity (∆G s φ,gas ),