Elongation dynamics of amyloid fibrils: a rugged energy landscape picture

TL;DR

This paper investigates the elongation process of amyloid fibrils using simulations, revealing a rugged energy landscape with local minima that affect monomer recycling, contrasting with traditional models.

Contribution

It introduces a novel rugged energy landscape perspective for amyloid fibril elongation based on Langevin dynamics simulations of a coarse-grained peptide model.

Findings

Elongation involves local minima due to interaction frustration.

Monomer recycling at fibril ends is significantly reduced.

The model's predictions can be experimentally tested.

Abstract

Protein amyloid fibrils are a form of linear protein aggregates that are implicated in many neurodegenerative diseases. Here, we study the dynamics of amyloid fibril elongation by performing Langevin dynamic simulations on a coarse-grained model of peptides. Our simulation results suggest that the elongation process is dominated by a series of local minimum due to frustration in monomer-fibril interactions. This rugged energy landscape picture indicates that the amount of recycling of monomers at the fibrils' ends before being fibrilized is substantially reduced in comparison to the conventional two-step elongation model. This picture, along with other predictions discussed, can be tested with current experimental techniques.