Document Detail


A multidimensional view of amyloid fibril nucleation in atomistic detail.
MedLine Citation:
PMID:  22276669     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Starting from a disordered aggregate, we have simulated the formation of ordered amyloid-like beta structures in a system formed by 18 polyvaline chains in explicit solvent, employing molecular dynamics accelerated by bias-exchange metadynamics. We exploited 8 different collective variables to compute the free energy of hundreds of putative aggregate structures, with variable content of parallel and anti-parallel beta-sheets and different packing among the sheets. This allowed characterizing in detail a possible nucleation pathway for the formation of amyloid fibrils: first the system forms a relatively large ordered nucleus of anti-parallel beta-sheets, then a few parallel sheets start appearing. The relevant nucleation process culminates at this point: when a sufficient number of parallel sheets is formed, the free energy starts to decrease towards a new minimum in which this structure is predominant. The complex nucleation pathway we found cannot be described within classical nucleation theory, namely employing a unique simple reaction coordinate like the total content of beta-sheets.
Authors:
Fahimeh Baftizadeh; Xevi Biarnés; Fabio Pietrucci; Fabio Affinito; Alessandro Laio
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-24
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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