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Abstract Many small globular proteins exist in only two states—the physiologically relevant folded state and an inactive unfolded state. The active state is stabilized by numerous weak attractive contacts, including hydrogen bonds, other polar interactions, and the hydrophobic effect. Knowledge of these interactions is key to understanding the fundamental equilibrium thermodynamics of protein folding and stability. We focus on one such interaction, that between amide and aromatic groups. We provide a statistically convincing case for quantitative, linear entropy–enthalpy compensation in forming aromatic–amide interactions using published model compound transfer‐free energy data.
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Influence of immobilized cations on the thermodynamic signature of hydrophobic interactions at chemically heterogeneous surfaces
Hydrophobic interactions play a central role in bioinspired strategies for molecular self-assembly in water, yet how these interactions are encoded by chemically heterogeneous interfaces is poorly understood. We report an experimental investigation of the influence of immobilized polar groups (amine) and cations (ammonium and guanidinium) on enthalpic and entropic contributions to hydrophobic interactions mediated by methyl-terminated surfaces at temperatures ranging from 298 K to 328 K and pH values between 3.5 to 10.5. We use our measurements to calculate the change in free energy (and enthalpic and entropic components) that accompanies transfer of each surface from aqueous TEA containing 60 vol% methanol into aqueous TEA ( i.e. , transfer free energy that characterizes hydrophobicity). We find the thermodynamic signature of the pure methyl surface (positive transfer enthalpy and entropy) to be altered qualitatively by incorporation of amine or guanidinium groups into the surface (negative transfer enthalpy and near zero transfer entropy). In contrast, ammonium groups immobilized on a methyl surface do not change the thermodynamic signature of the hydrophobic interaction. Compensation of entropy and enthalpy is clearly evident in our results, but the overall trends in the transfer free energies are dominated by enthalpic effects. This observation and others lead us to hypothesize that the dominant effect of the immobilized charged or polar groups in our experiments is to influence the number or strength of hydrogen bonds formed by interfacial water molecules adjacent to the nonpolar domains. Overall, these results provide insight into entropy–enthalpy compensation at chemically heterogeneous surfaces, and generate hypotheses and a rich experimental dataset for further exploration via simulation.
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- PAR ID:
- 10149158
- Date Published:
- Journal Name:
- Molecular Systems Design & Engineering
- ISSN:
- 2058-9689
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d0me00016g
