Exploring the temperature dependence of β-hairpin peptide self-assembly

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• Understanding the self-assembly of peptide amphiphiles is crucial for developing novel biomaterials.
• The role of hydrophobicity in temperature-dependent protein folding and peptide assembly is a key area of research.
• Existing computational tools may not offer sufficient resolution for detailed analysis of molecular interactions.

Purpose of the Study:

• To investigate the impact of hydrophobicity on the temperature-dependent self-assembly of β-hairpin peptide amphiphiles.
• To develop and utilize novel computational tools for measuring solvent-accessible charge (SAC) and solvent-accessible hydrophobicity (SAH).
• To compare the assembly behavior of peptides with varying SAH values and relate it to protein folding principles.

Main Methods:

• Development of computational tools to quantify solvent-accessible charge (SAC) and solvent-accessible hydrophobicity (SAH) at the atomic group level.
• Analysis of thermal assembly transitions in β-hairpin peptide amphiphiles with different SAH values.
• Correlation of SAH values with transition midpoints (T_g) for monomeric peptide to fibril transitions.

Main Results:

• Peptides with higher SAH values exhibit self-assembly into β-sheet-rich fibers at lower temperatures and faster rates.
• The hydrophobic effect, involving the release of ordered water, is identified as a primary driver for peptide assembly.
• A linear correlation was observed between SAH values and T_g for peptides with similar charge, indicating predictable assembly behavior.

Conclusions:

• Hydrophobicity is a critical determinant of the kinetics and thermodynamics of peptide amphiphile self-assembly.
• The developed computational methods provide a high-resolution approach to study molecular interactions in self-assembly processes.
• While entropy drives assembly, other thermodynamic factors also influence the precise transition temperatures, suggesting complex assembly mechanisms.