Denaturation of proteins: electrostatic effects vs. hydration

Abstract

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.