Chiral structure fluctuations predicted by a coarse-grained model of peptide aggregation

Area of Science:

• Biophysics
• Computational Chemistry
• Materials Science

Background:

• Peptide aggregation is central to various diseases and material applications.
• Understanding early aggregation stages, including structural dynamics, is crucial.
• Current models often simplify or overlook chiral dynamics in peptide clusters.

Purpose of the Study:

• To investigate chiral structure fluctuations in peptide clusters during early aggregation.
• To develop a model that captures these dynamics and their dependence on cluster size.
• To explore the potential role of chiral fluctuations in determining final aggregate morphology.

Main Methods:

• Coarse-grained molecular dynamics simulations of peptide clusters.
• Quantification of chiral fluctuations using a novel cluster twist parameter.
• Development of a simplified stochastic model for twist parameter dynamics.

Main Results:

• The peptide model reproduced diverse experimental aggregate structures.
• Simulations revealed spontaneous chiral structure fluctuations in small peptide clusters.
• A 1D potential surface model showed semi-quantitative agreement with simulation results for twist parameter diffusion.
• The potential surface's shape varied with cluster size.

Conclusions:

• Chiral structure fluctuations occur in peptide clusters even without explicit chirality in the solvent model.
• The developed stochastic model provides insights into the dynamics of these chiral fluctuations.
• Early-stage chiral fluctuations are hypothesized to be a key factor in selecting final peptide fibril structures.