Extension of the theory of linked functions to incorporate the effects of protein hydration

The effect of a low-molecular weight substance on a macromolecular equilibrium may result from changes in hydration that accompany the macromolecular reaction, as well as from changes in the extent of binding of the added substance. An effect observed at low concentrations of the added substances (e.g. allosteric effects in enzyme control) is almost certainly the result of binding of the added substance, as has heretofore been suggested; but changes in hydration are likely to have an important role in effects observed at high concentrations of the added substance (e.g. the dissociation of hemoglobin by the addition of salt).