Entropy and enthalpy convergence of hydrophobic solvation beyond the hard-sphere limit

Abstract

The experimentally well-known convergence of solvation entropies and enthalpies of different small hydrophobic solutes at universal temperatures seems to indicate that hydrophobic solvation is dominated by universal water features and not so much by solute specifics. The reported convergence of the denaturing entropy of a group of different proteins at roughly the same temperature as hydrophobic solutes was consequently argued to indicate that the denaturing entropy of proteins is dominated by the hydrophobic effect and used to estimate the hydrophobic contribution to protein stability. However, this appealing picture was subsequently questioned since the initially claimed universal convergence of denaturing entropies holds only for a small subset of proteins; for a larger data collection no convergence is seen. We report extensive simulation results for the solvation of small spherical solutes in explicit water with varying solute-water potentials. We show that convergence of solvation properties for solutes of different radii exists but that the convergence temperatures depend sensitively on solute-water potential features such as stiffness of the repulsive part and attraction strength, not so much on the attraction range. Accordingly, convergence of solvation properties is only expected for solutes of a homologous series that differ in the number of one species of subunits (which attests to the additivity of solvation properties) or solutes that are characterized by similar solute-water interaction potentials. In contrast, for peptides that arguably consist of multiple groups with widely disperse interactions with water, it means that thermodynamic convergence at a universal temperature cannot be expected, in general, in agreement with experimental results.

Solvation thermodynamics of amino acid side chains on a short peptide backbone

“…In contrast, the entropy (T∆S S ) and enthalpy (∆H S ) changes of solvating nonpolar solutes in water at room temperature are both negative but increase rapidly with increasing temperature. [4][5][6][7][8] The stronger temperature dependence of the latter two quantities is owing to a dominant contribution of solvent reorganization, which, despite its significance in understanding heat capacity effects, 9 does not affect the solvation free energy due to exact enthalpy-entropy compensation. 10-12 a) Author to whom correspondence should be addressed.…”

Water anomalous thermodynamics, attraction, repulsion, and hydrophobic hydration

“…Furthermore, the present results agree with some well-established experimental observations. 11 Specifically, T * S > T * H , s * p (T * S ) is small in magnitude for hydrophobic solutes, and a variety of solutes in water, including pure hydrophobes and amphiphiles, exhibit both enthalpy and entropy convergence.…”

“…With explicit expressions for all those derivatives listed in Appendix B, we fixed the mole fraction of solute in solution ρ 2 /ρ and solved numerically Eqs. (11) and (12) for T and ρ 1 . From the resulting T c (ρ 2 /ρ) and ρ 1,c (ρ 2 /ρ), the corresponding critical pressure p c (ρ 2 /ρ) is determined by solving (B4).…”

“…In addition, the solvation entropy for solutes of varying size has been found to take nearly the same value at a temperature known as the convergence temperature. Specifically, entropy convergence as well as its enthalpic counterpart have been experimentally observed for a variety of families of nonpolar solutes 11 while it has been pointed out that proteins also display such phenomena, 11,12 this being one of the reasons why a strong connection between hydrophobicity and protein thermodynamics has been suggested (see, e.g., Ref. 9).…”

Cold denaturation of RNA secondary structures with loop entropy and quenched disorder

“…Denaturation when lowering the temperature is usually interpreted in terms of hydrophobic interactions. Experimentally, denaturation can be inferred by the presence of peaks in the specific heat which physically follow from an abrupt increase of the system entropy [7][8][9][10]. In this paper we give an alternative explanation for cold denaturation in terms of quenched disorder which itself weakens the secondary structure formation at low temperature.…”