Solvent denaturation and stabilization of globular proteins.

Area of Science:

• Thermodynamics
• Protein Folding
• Biophysical Chemistry

Background:

• Recent advances in statistical thermodynamic theory explain globular protein stability.
• Protein folding is influenced by solvophobic interactions and conformational entropy.

Purpose of the Study:

• To extend existing thermodynamic theory to predict solvent effects on protein stability.
• To investigate the impact of urea and guanidine hydrochloride (GuHCl) on protein denaturation.

Main Methods:

• Utilizing statistical thermodynamic theory based on solvophobic interactions.
• Incorporating transfer experiments of amino acids into aqueous solutions of urea and GuHCl.
• Modeling protein folding via two pathways: collapse and core formation.

Main Results:

• Predicted two-state denaturation transitions with increasing denaturant concentration.
• Denaturation midpoints occur at higher urea concentrations than GuHCl.
• The radius of the solvent-denatured state is smaller than a random-flight chain and increases with denaturant or polar residues.
• Free energy of folding is linear for urea but shows slight curvature for GuHCl.
• Predicted slopes and exposed areas of unfolded states generally agree with experimental findings.

Conclusions:

• The extended thermodynamic theory accurately predicts solvent effects on protein stability.
• The model provides insights into denaturation mechanisms and the behavior of unfolded protein states.
• Comparison of thermal and solvent denaturation is discussed, along with stabilizing solvents.