Discrete molecular dynamics simulations of peptide aggregation

TL;DR

This study uses discrete molecular dynamics simulations to investigate peptide aggregation, revealing beta-sheet structures consistent with experimental data and highlighting the roles of hydrogen bonds and side-chain interactions.

Contribution

It introduces a discrete molecular dynamics model that accurately reproduces peptide aggregation structures and mechanisms observed experimentally.

Findings

Peptides form multi-layer parallel beta-sheets above melting temperature.

Inter-strand distance of 0.48 nm matches experimental data.

Aggregates contain free edges that could lead to fibril formation.

Abstract

We study the aggregation of peptides using the discrete molecular dynamics simulations. At temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multi-layer parallel beta-sheet structure. This structure has an inter-strand distance of 0.48 nm and an inter-sheet distance of 1.0 nm, which agree with experimental observations. In this model, the hydrogen bond interactions give rise to the inter-strand spacing in beta-sheets, while the Go interactions among side chains make beta-strands parallel to each other and allow beta-sheets to pack into layers. The aggregates also contain free edges which may allow for further aggregation of model peptides to form elongated fibrils.