Solvent effects on protein association and protein folding

Area of Science:

• Biochemistry
• Physical Chemistry
• Computational Biology

Background:

• Solvent effects significantly influence protein folding and association thermodynamics.
• Understanding these effects is crucial for predicting protein behavior and function.
• Existing models often oversimplify the complex interactions between solvents and protein residues.

Purpose of the Study:

• To comprehensively examine solvent effects on protein folding and association thermodynamics.
• To introduce and apply the concept of conditional solvation free energy for detailed analysis.
• To evaluate the adequacy of current hydrophobicity scales and explore alternative correlation models.

Main Methods:

• Utilizing the theoretical framework of conditional solvation free energy.
• Analyzing small model compounds to isolate specific side-chain contributions.
• Presenting numerical examples and suggesting methods for estimating data where experimental results are unavailable.

Main Results:

• Conditional solvation free energy provides a complete inventory of solvent effects.
• Current hydrophobicity scales are inadequate for assessing side-chain transfer to protein interiors.
• Hydrophilic group correlations may play a more significant role than hydrophobic side-chain correlations.

Conclusions:

• Rethinking current hydrophobicity scales is necessary for accurate thermodynamic predictions.
• Focusing on hydrophilic interactions could offer new insights into protein stability and assembly.
• Conditional solvation free energy is a powerful tool for dissecting complex solvent-protein interactions.