Selective binding and solvent denaturation

TLDR

A primitive model of solvent denaturation assumes denaturants bind independently to exposed sites, but for urea and guanidinium salts this binding must be very weak, leading to thermodynamic inconsistencies in standard weak‑binding formulas. The study treats denaturant binding as selective solvation. The model incorporates a factor K1 in the binding isotherm and free energy, where K is the equilibrium constant for selective interaction with sites. The resulting description is thermodynamically consistent, predicting no denaturation effect when K = 1 even at high denaturant concentrations.

Abstract

Abstract A primitive model for solvent denaturation is that the denaturant binds independently to sites exposed by the unfolding of the protein. For reagents like urea and guanidinium salts, this binding must be very weak since denaturation occurs only at very high concentrations. Standard formulas for very weak binding lead to thermodynamic inconsistencies. In this paper, binding by denaturants is treated as selective solvation. This introduces a factor of K 1 into the binding isotherm and binding free energy, where K is the equilibrium constant for selective interaction with the sites. This leads to a thermodynamically consistent description of the binding and the denaturation since, when K = 1, there is no selective interaction and no effect on denaturation, even in concentrated solutions where site occupancy is inevitable.