Structures of soluble amyloid oligomers from computer simulations

Adrien Melquiond, Normand Mousseau, Philippe Derreumaux

Research output: Contribution to journalArticleAcademicpeer-review


Alzheimer's, Parkinson's, and Creutzfeldt-Jakob's neurodegenerative diseases are all limited with the assembly of normally soluble proteins into amyloid fibrils. Because of experimental limitations, structural characterization of the soluble oligomers, which form early in the process of fibrillogenesis and are cytotoxic, remains to be determined. In this article, we study the aggregation paths of seven chains of the shortest amyloid-forming peptide, using an activitated method and a reduced atomic representation. Our simulations show that disordered KFFE monomers ultimately form three distinct topologies of similar energy: amorphous oligomers, incomplete rings with β-barrel character, and cross-β-sheet structures with the meridional but not the equatorial X-ray fiber reflections. The simulations also shed light on the pathways from misfolded aggregates to fibrillar-like structures. They also underline the multiplicity of building blocks that can lead to the formation of the critical nucleus from which rapid growth of the fibril occurs. © 2006 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)180-191
Number of pages12
JournalProteins: Structure, Function and Genetics
Issue number1
Publication statusPublished - 1 Oct 2006
Externally publishedYes


  • Activation-relaxation technique
  • Aggregation
  • Amyloid fibril formation
  • Coarse-grained force field
  • Molecular dynamics
  • Protein simulations
  • Soluble oligomers
  • amyloid
  • activation relaxation technique
  • Alzheimer disease
  • amyloidosis
  • article
  • beta sheet
  • computer simulation
  • Creutzfeldt Jakob disease
  • cytotoxicity
  • degenerative disease
  • efficient peptide structure prediction
  • molecular dynamics
  • oligomerization
  • Parkinson disease
  • priority journal
  • protein aggregation
  • protein structure
  • structure analysis


Dive into the research topics of 'Structures of soluble amyloid oligomers from computer simulations'. Together they form a unique fingerprint.

Cite this