Energetics of protein folding

Area of Science:

• Biochemistry and Molecular Biology
• Computational Biology

Background:

• Protein folding determines a protein's 3D structure, crucial for its function.
• Predicting protein structure from amino acid sequence and engineering protein modifications require knowledge of folding energetics.

Purpose of the Study:

• To review recent developments in understanding protein folding energetics.
• To discuss major and auxiliary factors influencing protein folding.
• To highlight advancements in modeling hydrophobic effects, hydrogen bonds, and solvation.

Main Methods:

• Review of recent energetic studies on peptide hydrogen bonds and solvation.
• Analysis of models for hydrophobic effects, including the packing-desolvation model.
• Comparison of theoretical calculations for protein unfolding enthalpies.

Main Results:

• The hydrophobic factor, van der Waals interactions, peptide hydrogen bonds, and solvation are major contributors to folding energetics.
• Contrasting the traditional surface area model with the packing-desolvation model for hydrophobic effects.
• Improved agreement in calculated protein unfolding enthalpies when solvation effects are considered.

Conclusions:

• Accurate prediction of protein 3D structure and effective protein engineering rely on a comprehensive understanding of folding energetics.
• Recent studies refine the understanding of hydrophobic effects and peptide solvation, leading to more accurate energetic predictions.
• Further research is needed to fully elucidate the role of auxiliary factors and backbone conformational entropy in protein folding.