Denaturation of proteins: electrostatic effects vs. hydration

Area of Science:

• Biophysics
• Protein chemistry
• Physical chemistry

Background:

• Protein unfolding in solution is a fundamental biophysical process.
• Solutes significantly alter protein transition temperature (Tm).
• Existing models do not fully capture solute effects on protein unfolding.

Purpose of the Study:

• To present a phenomenological model describing how solute concentration (cs) affects protein transition temperature (Tm).
• To elucidate the roles of counterion (Δnci) and hydration (Δw) changes in solute-induced Tm shifts.
• To provide a unified framework for understanding ionic and hydration contributions to protein stability.

Main Methods:

• Development of a phenomenological model based on thermodynamic principles.
• Incorporation of counterion binding/release (Δnci) and water interaction (Δw) as key parameters.
• Analysis of the temperature dependence of hydration effects (dΔcp/dcs).

Main Results:

• The model quantiqualitatively describes Tm changes with solute concentration (cs).
• Counterion effects (Δnci) are entropic and salt-independent.
• Hydration effects (Δw) are enthalpic/entropic, temperature-dependent, and linked to Hofmeister series.
• The model's predictions align with experimental data from literature.

Conclusions:

• The presented model offers a comprehensive explanation for solute effects on protein unfolding temperature.
• It distinguishes between salt-dependent hydration and salt-independent ionic contributions.
• The model's general validity is supported by comparison with existing experimental findings.