Protein Denaturation Zero Entropy Temperature, and the Structure of Water Around Hydrophobic and Amphiphilic Solutes

Abstract

The hydrophobic effect plays a key role in many chemical and biological processes, including protein folding. Nonetheless, a comprehensive picture of the effect of temperature on hydrophobic hydration and protein denaturation remains elusive. Here, we study the effect of temperature on the hydration of model hydrophobic and amphiphilic solutes through molecular dynamics aiming at getting in sight on the singular behavior of water concerning the zero entropy temperature TS and entropic convergence also observed upon protein denaturation. We show that, similar to hydrocarbons and proteins, polar amphiphilic solutes exhibit a TS, although strongly dependent upon solute-water interactions, opposite to hydrocarbons. Further, the temperature dependence of the hydration entropy normalized by the solvent accessible surface area is shown to be nearly solute size independent for hydrophobic but not for amphiphilic solutes, for similar reasons. These results are further discussed in the light of information theory (IT) and the structure of water around hydrophobic groups The latter shows that the tetrahedral enhancement of some water molecules around hydrophobic groups, associated with the reduction of water defects, leads to the strengthening of the weakest hydrogen bonds, relative to bulk water. However, a larger tetrahedrality is found in low density water populations, demonstrating that pure water has encoded structural information similar to that associated with hydrophobic hydration, consistent with IT assumptions. The source of the differences between Kauzmann's "hydrocarbon model" on protein denaturation and hydrophobic hydration is also discussed with relatively large amphiphilic hydrocarbons displaying a more similar behavior to globular proteins, than aliphatic hydrocarbons.<br>

Temperature, Pressure, and Length-Scale Dependence of Solvation in Water-like Solvents. I. Small Solvophobic Solutes

“…For the families of light hydrocarbons and noble gases, the negative u ̅ V * values arising from solute−solvent attractive interactions are of larger magnitude for larger solutes, 7 which makes the crossing of h̅ p *(T) curves to be expected to take place at temperatures higher than T MD . Such expectation is supported by detailed simulations 29 and experimental observations. 61,63 Another feature that characterizes enthalpy and entropy convergence is the v ̅ p range spanned by the solutes under consideration.…”

“…The h̅ p * ( T ) curves cross at low temperatures, whereas extrapolation of data for s̅ p * ( T ) curves suggests such curve crossing to occur at high temperatures well beyond our working range. This “enthalpy and entropy convergence” has been observed experimentally for aqueous solutions of families of solutes of varying size, ,− while it has been highlighted in connection with the thermodynamics of protein folding. − …”

“…The latter pertains to a family of model fluids characterized by isotropic pair potentials with two relevant energy scales that make them to exhibit water-like unusual thermodynamics . Accordingly, there is a strong suggestion that the corresponding thermodynamics of solvophobic solvation should reflect Jagla-fluid unusual thermodynamics just as the thermodynamics of aqueous solvation reflects that of water. , While previous work on this indicates that “Jagla-solvation is aqueous-like”, , it merits our attention to jointly approach isochoric and isobaric solvation for TIP4P/2005 and Jagla water-like solvents and thereby to expand the work on comparative studies of solvation in distinct solvents ,, as well as on the temperature and pressure dependence of solvation. − To this end, we report μ ̅ *­( T , p ), u̅ V * ( T , p ), s̅ V * ( T , p ), h̅ p * ( T , p ), s̅ p * ( T , p ), v p ( T , p ), and v̅ p ( T , p ) data as obtained from molecular simulation and analyze them with the aid of scaled-particle theory (SPT), the Gaussian model of small-length-scale solvation, ,, and our current knowledge of water-like thermodynamics. Methods are described in Section and results presented and thoroughly discussed in Section .…”