Document Detail

A multidimensional view of amyloid fibril nucleation in atomistic detail.
MedLine Citation:
PMID:  22276669     Owner:  NLM     Status:  Publisher    
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.
Fahimeh Baftizadeh; Xevi Biarnés; Fabio Pietrucci; Fabio Affinito; Alessandro Laio
Related Documents :
3002429 - Characterization of the oligosaccharides of prolyl hydroxylase, a microsomal glycoprotein.
19746469 - Alpha-o-linked glycopeptide mimetics: synthesis, conformation analysis, and interaction...
1769019 - Further structural studies of the carbohydrate moiety of the allergen ag-54 (cla h ii) ...
7669849 - Purification and partial characterization of acrosome reaction inhibiting glycoprotein ...
21302959 - Structure-based design of a heptavalent anthrax toxin inhibitor.
21199369 - Design of hairpin ribozyme variants with improved activity for poorly processed substra...
14640449 - Enantiomer separation of miconazole by capillary electrophoresis with dual cyclodextrin...
291029 - Subunit interaction during catalysis: alternating site cooperativity in photophosphoryl...
14690539 - Riboflavin synthase of schizosaccharomyces pombe. protein dynamics revealed by 19f nmr ...
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:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Surface Modification of Smooth Poly(L-lactic acid) Films for Gelatin Immobilization.
Next Document:  A Comparative Ab Initio Study of the Primary Hydration and Proton Dissociation of Various Imide and ...