Interplay between the hydrophobic effect and dipole interactions in peptide aggregation at interfaces

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• Protein misfolding and aggregation are fundamental processes with implications in disease and biomaterials.
• Coarse-grained models are crucial for understanding protein folding and aggregation dynamics.
• Previous models lacked sufficient detail to capture essential structural features and interactions.

Purpose of the Study:

• To extend the Water Explicit Polarizable PROtein coarse-grained Model (WEPPROM) for studying peptide aggregation at interfaces.
• To compare peptide aggregation mechanisms in explicit water versus at hydrophobic-hydrophilic interfaces.
• To elucidate the driving forces behind fibril-like peptide aggregation.

Main Methods:

• Development and application of the WEPPROM, incorporating oppositely charged dummy particles in backbone beads.
• Simulation of elastin-like octapeptides (GV)4 aggregation in explicit water and at interfaces.
• Analysis of aggregation mechanisms, focusing on the role of dipolar interactions and hydrophobicity.

Main Results:

• A condensation-ordering aggregation mechanism was observed in water.
• Backbone interpeptide dipolar interactions were identified as a primary driver of fibril-like peptide aggregation, surpassing hydrophobicity.
• A cooperative effect in hydrogen bonding and dipolar interactions was noted, increasing aggregate size and aggregation rate at interfaces.
• Peptide aggregation at interfaces was absent without the inclusion of dipolar particles in the model.

Conclusions:

• Dipolar interactions, rather than hydrophobicity, are key to peptide aggregation at hydrophobic interfaces.
• The WEPPROM effectively models peptide aggregation, providing insights into nucleus size and cooperative effects.
• Hydrophobic-hydrophilic interfaces enhance the order and rate of peptide aggregation through cooperative interactions.