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Structural diversity and initial oligomerization of PrP106-126 studied by replica-exchange and conventional molecular dynamics simulations
- Source :
- PLoS ONE, Vol 9, Iss 2, p e87266 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Prion diseases are marked by cerebral accumulation of the abnormal isoform of the prion protein. A fragment of prion protein composed of residues 106-126 (PrP106-126) exhibits similar properties to full length prion and plays a key role in the conformational conversion from cellular prion to its pathogenic pattern. Soluble oligomers of PrP106-126 have been proposed to be responsible for neurotoxicity. However, the monomeric conformational space and initial oligomerization of PrP106-126 are still obscure, which are very important for understanding the conformational conversion of PrP106-126. In this study, replica exchange molecular dynamics simulations were performed to investigate monomeric and dimeric states of PrP106-126 in implicit solvent. The structural diversity of PrP106-126 was observed and this peptide did not acquire stable structure. The dimeric PrP106-126 also displayed structural diversity and hydrophobic interaction drove the dimerization. To further study initial oligomerization of PrP106-126, 1 µs conventional molecular dynamics simulations of trimer and tetramer formation were carried out in implicit solvent. We have observed the spontaneous formation of several basic oligomers and stable oligomers with high β-sheet contents were sampled in the simulations of trimer and tetramer formation. The β-hairpin formed in hydrophobic tail of PrP106-126 with residues 118-120 in turn may stabilize these oligomers and seed the formation oligomers. This study can provide insight into the detailed information about the structure of PrP106-126 and the dynamics of aggregation of monomeric PrP106-126 into oligomers in atomic level.
- Subjects :
- Proteomics
Protein Structure
Prions
Science
Trimer
Peptide
Molecular Dynamics Simulation
Bioinformatics
Biochemistry
Protein Structure, Secondary
Prion Diseases
Turn (biochemistry)
Hydrophobic effect
chemistry.chemical_compound
Molecular dynamics
Tetramer
Macromolecular Structure Analysis
Humans
Molecule
Amino Acid Sequence
Protein Interactions
Biology
chemistry.chemical_classification
Multidisciplinary
Zoonotic Diseases
Proteins
Computational Biology
Peptide Fragments
Infectious Diseases
Monomer
Veterinary Diseases
chemistry
Protein Classes
Biophysics
Medicine
Veterinary Science
Protein Multimerization
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....91a3dd6b7d9d5feed559a2964d9aee27