Denaturation of proteins: electrostatic effects vs. hydration

The unfolding transition of proteins in aqueous solution containing various salts or uncharged solutes is a classical subject of biophysics. In many cases, this transition is a well-defined two-stage equilibrium process which can be described by a free energy of transition ΔG _u and a transition temperature T _m. For a long time, it has been known that solutes can change T _m profoundly. Here we present a phenomenological model that describes the change of T _m with the solute concentration c _s in terms of two effects: (i) the change of the number of correlated counterions Δn _ci and (ii) the change of hydration expressed through the parameter Δw and its dependence on temperature expressed through the parameter dΔc _p/dc _s. Proteins always carry charges and Δn _ci describes the uptake or release of counterions during the transition. Likewise, the parameter Δw measures the uptake or release of water during the transition. The transition takes place in a reservoir with a given salt concentration c _s that defines also the activity of water. The parameter Δn _ci is a measure for the gain or loss of free energy because of the release or uptake of ions and is related to purely entropic effects that scale with ln c _s. Δw describes the effect on ΔG _u through the loss or uptake of water molecules and contains enthalpic as well as entropic effects that scale with c _s. It is related to the enthalpy of transition ΔH _u through a Maxwell relation: the dependence of ΔH _u on c _s is proportional to the dependence of Δw on temperature. While ionic effects embodied in Δn _ci are independent of the kind of salt, the hydration effects described through Δw are directly related to Hofmeister effects of the various salt ions. A comparison with literature data underscores the general validity of the model.