Home LiteratureArticle Details
PMID: 15534217 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 46 ·2004-11-16 ·Pages 16180-5

Nguyen HD, Hall CK

Abstract

Assembly of normally soluble proteins into amyloid fibrils is a cause or associated symptom of numerous human disorders, including Alzheimer's and the prion diseases. We report molecular-level simulation of spontaneous fibril formation. Systems containing 12-96 model polyalanine peptides form fibrils at temperatures greater than a critical temperature that decreases with peptide concentration and exceeds the peptide's folding temperature, consistent with experimental findings. Formation of small amorphous aggregates precedes ordered nucleus formation and subsequent rapid fibril growth through addition of beta-sheets laterally and monomeric peptides at fibril ends. The fibril's structure is similar to that observed experimentally.

MeSH Terms
Amyloid/chemistry Biophysical Phenomena Biophysics Humans In Vitro Techniques Models, Molecular Multiprotein Complexes Peptides/chemistry Thermodynamics
Chemicals
Amyloid Multiprotein Complexes Peptides polyalanine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nguyen Hung D
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695-7905, USA.
Hall Carol K
References (28)
28 references, click to expand
  1. Biophysical studies of the development of amyloid fibrils from a peptide fragment of cold shock protein B.
    Eur J Biochem. 2000 May;267(9):2609-16 PMID: 10785381
  2. Amyloid diseases: abnormal protein aggregation in neurodegeneration.
    Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):9989-90 PMID: 10468546
  3. Nucleated conformational conversion and the replication of conformational information by a prion determinant.
    Science. 2000 Aug 25;289(5483):1317-21 PMID: 10958771
  4. Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.
    Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13045-50 PMID: 11069287
  5. The structural basis of protein folding and its links with human disease.
    Philos Trans R Soc Lond B Biol Sci. 2001 Feb 28;356(1406):133-45 PMID: 11260793
  6. Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates.
    Biochemistry. 2001 Mar 27;40(12):3525-35 PMID: 11297418
  7. alpha-helix formation: discontinuous molecular dynamics on an intermediate-resolution protein model.
    Proteins. 2001 Aug 15;44(3):344-60 PMID: 11455608
  8. Assembly of a tetrameric alpha-helical bundle: computer simulations on an intermediate-resolution protein model.
    Proteins. 2001 Aug 15;44(3):376-91 PMID: 11455611
  9. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases.
    Nature. 2002 Apr 4;416(6880):507-11 PMID: 11932737
  10. Towards an understanding of amyloidogenesis.
    Nat Struct Biol. 2002 May;9(5):323-5 PMID: 11976724
  11. Supramolecular structure in full-length Alzheimer's beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance.
    Biophys J. 2002 Aug;83(2):1205-16 PMID: 12124300
  12. Amyloid-fibril formation. Proposed mechanisms and relevance to conformational disease.
    Eur J Biochem. 2002 Jul;269(14):3362-71 PMID: 12135474
  13. Molecular dynamics simulations of alanine rich beta-sheet oligomers: Insight into amyloid formation.
    Protein Sci. 2002 Oct;11(10):2335-50 PMID: 12237456
  14. Solvent environment conducive to protein aggregation.
    FEBS Lett. 2002 Oct 9;529(2-3):298-301 PMID: 12372617
  15. Dissecting the assembly of Abeta16-22 amyloid peptides into antiparallel beta sheets.
    Structure. 2003 Mar;11(3):295-307 PMID: 12623017
  16. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis.
    Science. 2003 Apr 18;300(5618):486-9 PMID: 12702875
  17. The role of side-chain interactions in the early steps of aggregation: Molecular dynamics simulations of an amyloid-forming peptide from the yeast prion Sup35.
    Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5154-9 PMID: 12700355
  18. Human amylin oligomer growth and fibril elongation define two distinct phases in amyloid formation.
    J Biol Chem. 2004 Mar 26;279(13):12206-12 PMID: 14704152
  19. Solvent effects on the conformational transition of a model polyalanine peptide.
    Protein Sci. 2004 Nov;13(11):2909-24 PMID: 15498937
  20. X-ray diffraction studies of fibrils formed from peptide fragments of transthyretin.
    Biochem Biophys Res Commun. 1993 May 14;192(3):991-8 PMID: 8507211
  21. Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.
    J Biol Chem. 1994 Nov 18;269(46):28551-4 PMID: 7961799
  22. Parallel beta-domains: a new fold in protein structures.
    Curr Opin Struct Biol. 1994 Dec;4(6):802-6 PMID: 7712282
  23. Formation of an extremely stable polyalanine beta-sheet macromolecule.
    Biochem Biophys Res Commun. 1995 Jun 6;211(1):7-13 PMID: 7779112
  24. Common core structure of amyloid fibrils by synchrotron X-ray diffraction.
    J Mol Biol. 1997 Oct 31;273(3):729-39 PMID: 9356260
  25. Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer's disease amyloid-beta protein.
    Chem Biol. 1997 Dec;4(12):951-9 PMID: 9427660
  26. Structural analysis of Alzheimer's beta(1-40) amyloid: protofilament assembly of tubular fibrils.
    Biophys J. 1998 Jan;74(1):537-45 PMID: 9449354
  27. Propagating structure of Alzheimer's beta-amyloid(10-35) is parallel beta-sheet with residues in exact register.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13407-12 PMID: 9811813
  28. The protofilament substructure of amyloid fibrils.
    J Mol Biol. 2000 Jul 28;300(5):1033-9 PMID: 10903851
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0407273101
Published
2004-11-16
Epub
2004-00-08
Pages
16180-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC526199
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056766 · United States
NIGMS NIH HHS · GM-56766 · United States
External Links
PubMed source DOI: 10.1073/pnas.0407273101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2