Long-Range Interactions Dominate the Inverse-Temperature Dependence of Polypeptide Hydration Free Energies

TL;DR

This study uses detailed all-atom calculations to show that attractive interactions and solvent expansion, rather than hydrophobic effects, primarily explain the inverse temperature dependence of polypeptide hydration free energies.

Contribution

It reveals that long-range interactions and solvent effects are key factors, challenging traditional hydrophobic explanations for protein stability.

Findings

Attractive interactions dominate hydration free energies.

Thermal expansion of water influences inverse temperature dependence.

Hydrophobic mechanisms are less significant than previously thought.

Abstract

Direct, all-atom calculations of the free energy of hydration of aqueous deca-alanine structures --- holistically including backbone and side-chain interactions together --- show that attractive interactions and the thermal expansion of the solvent explain the inverse temperature signatures that have been interpreted traditionally in favor of hydrophobic mechanisms for stabilizing the structure and function of soluble proteins.