Using 19F NMR to quantify enthalpy-entropy compensation in protein-protein interactions.

Protein structural, stability, and functional equilibria are sensitive to the solution environment and governed by enthalpic and entropic contributions. NMR spectroscopy of suitably labeled- or isotopically enriched-samples provides a powerful tool for quantifying protein reactions in solution. Here we apply 19F NMR data, acquired in a systematic effort to assess the equilibrium crowding effects of polyethylene glycols (PEGs), to reveal the first quantitative evidence for enthalpy-entropy compensation in protein-protein complexes. Analysis of the effects of PEG molecular weight and concentration reveals that changes in polymer -mesh size and -concentration produce proportional, compensatory shifts in the enthalpic and entropic components of dimer dissociation.