Modeling the solvation of nonpolar amino acids in guanidinium chloride solutions.

It is common to denature proteins by using high temperatures or by adding guanidinium chloride (GdmCl). However, the physical mechanism of denaturation is not well understood. Based on extensive experimental data, we developed a thermodynamic binding-polynomial model for the process of transferring nonpolar amino acids from water into GdmCl solutions, as a function of temperature and GdmCl concentration. To mimic nonpolar amino acids, we utilized the model compound, N-acetyl-tryptophanamide (NATA). We find that all nonpolar amino acids behave like NATA, with a scale factor linearly dependent on the surface area. Our model with three thermodynamic parameters fully captures the nonlinear dependencies on both the temperature and GdmCl concentration: binding the first guanidinium ion (Gdm(+)) to NATA has favorable entropy and unfavorable enthalpy of desolvation (ΔS = +11.7 cal/mol, ΔH = +3.9 kcal/mol), while cooperativity of binding a second Gdm(+) has a small contribution (K = 0.032 ± 0.003). This model may be useful for a better understanding of protein denaturation by temperature and GdmCl.