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Principles governing oligomer formation in amyloidogenic peptides

Authors
Journal
Current Opinion in Structural Biology
0959-440X
Publisher
Elsevier
Publication Date
Volume
20
Issue
2
Identifiers
DOI: 10.1016/j.sbi.2009.12.017
Disciplines
  • Biology

Abstract

Identifying the principles that describe the formation of protein oligomers and fibrils with distinct morphologies is a daunting problem. Here we summarize general principles of oligomer formation gleaned from molecular dynamics simulations of A β -peptides. The spectra of high free energy structures sampled by the monomer provide insights into the plausible fibril structures, providing a rationale for the ‘strain phenomenon.’ Heterogeneous growth dynamics of small oligomers of A β 16 – 22 , whose lowest free energy structures are like nematic droplets, can be broadly described using a two-stage dock-lock mechanism. In the growth process, water is found to play various roles depending on the oligomer size, and peptide length, and sequence. Water may be an explicit element of fibril structure linked to various fibril morphologies.

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