Molecular Dynamics Simulations of Spontaneous Fibril Formation by Random-Coil Peptides

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 f...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 101; no. 46; pp. 16180 - 16185
Main Authors Nguyen, Hung D., Hall, Carol K., Prausnitz, John M.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 16.11.2004
National Acad Sciences
Subjects
Amyloid - chemistry
Amyloids
Atoms
Biological Sciences
Biophysical Phenomena
Biophysics
Critical temperature
Disease
Duchenne muscular dystrophy
High temperature
Humans
Hydrogen
Hydrogen bonds
In Vitro Techniques
Modeling
Models, Molecular
Molecular dynamics
Molecular structure
Multiprotein Complexes
Peptides
Peptides - chemistry
Solar fibrils
Temperature
Thermodynamics
Online AccessGet full text

Cover

More Information
Summary: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 β-sheets laterally and monomeric peptides at fibril ends. The fibril's structure is similar to that observed experimentally.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Abbreviations: DMD, discontinuous molecular dynamics; PRIME, Protein Intermediate-Resolution Model.
Author contributions: H.D.N. and C.K.H. designed research, performed research, analyzed data, and wrote the paper.
Communicated by John M. Prausnitz, University of California, Berkeley, CA, October 1, 2004
To whom correspondence should be addressed. E-mail: hall@turbo.che.ncsu.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0407273101