Fibril fragments from the amyloid core of lysozyme: An accelerated molecular dynamics study

Protein aggregation and formation of amyloid fibrils are associated with many diseases and present a ubiquitous problem in protein science. Hen egg white lysozyme (HEWL) can form fibrils both from the full length protein and from its fragments. In the present study, we simulated unfolding of the amy-loidogenic fragment of HEWL encompassing residues 49-101 to study the conformational aspects of amyloidogenesis. The accelerated molecular dynamics approach was used to speed up the sampling of the fragment conformers under enhanced temperature. Analysis of conformational transformation and intermediate structures was performed. During the unfolding, the novel short-living and long-living 13-structures are formed along with the unstructured random coils. Such 13-structure enriched monomers can interact with each other and propagate into fibril-like forms. The stability of oligomers assembled from these monomers was evaluated in the course of MD simulations with explicit water. The residues playing a key role in fibril stabilization were determined. The work provides new insights into the processes occurring at the early stages of amyloid fibril assembly. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study simulated the unfolding of the amyloidogenic fragment of HEWL, revealing the formation of novel structures during the process that can contribute to the assembly of oligomers and propagate into fibril-like forms.