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Effects of Macromolecular Crowding on Amyloid Beta (16-22) Aggregation Using Coarse-Grained Simulations

Title
Effects of Macromolecular Crowding on Amyloid Beta (16-22) Aggregation Using Coarse-Grained Simulations
Authors
Latshaw, DC[Latshaw, David C.]Cheon, M[Cheon, Mookyung]Hall, CK[Hall, Carol K.]
DGIST Authors
Cheon, M[Cheon, Mookyung]
Issue Date
2014-11-27
Citation
Journal of Physical Chemistry B, 118(47), 13513-13526
Type
Article
Article Type
Article
Keywords
AmyloidAmyloid Beta-PeptidesAmyloid Beta-Protein (16-22)Amyloid Beta ProteinChemistryComputer SimulationConformational ConversionDimersDiscontinuous Molecular Dynamics SimulationsEnhancement EffectsInformation DisseminationKineticsMacromolecular CrowdingMolecular DynamicsMolecular Dynamics SimulationNucleated PolymerizationOligomer FormationsPeptide FragmentPeptide FragmentsPeptidesProtein AggregationProtein ModelingProtein MultimerizationVolume Fraction
ISSN
1520-6106
Abstract
To examine the effect of crowding on protein aggregation, discontinuous molecular dynamics (DMD) simulations combined with an intermediate resolution protein model, PRIME20, were applied to a peptide/crowder system. The systems contained 192 Aβ(16-22) peptides and crowders of diameters 5, 20, and 40 Å, represented here by simple hard spheres, at crowder volume fractions of 0.00, 0.10, and 0.20. Results show that both crowder volume fraction and crowder diameter have a large impact on fibril and oligomer formation. The addition of crowders to a system of peptides increases the rate of oligomer formation, shifting from a slow ordered formation of oligomers in the absence of crowders, similar to nucleated polymerization, to a fast collapse of peptides and subsequent rearrangement characteristic of nucleated conformational conversion with a high maximum in the number of peptides in oligomers as the total crowder surface area increases. The rate of conversion from oligomers to fibrils also increases with increasing total crowder surface area, giving rise to an increased rate of fibril growth. In all cases, larger volume fractions and smaller crowders provide the greatest aggregation enhancement effects. We also show that the size of the crowders influences the formation of specific oligomer sizes. In our simulations, the 40 Å crowders enhance the number of dimers relative to the numbers of trimers, hexamers, pentamers, and hexamers, while the 5 Å crowders enhance the number of hexamers relative to the numbers of dimers, trimers, tetramers, and pentamers. These results are in qualitative agreement with previous experimental and theoretical work. © 2014 American Chemical Society.
URI
http://hdl.handle.net/20.500.11750/3000
DOI
10.1021/jp508970q
Publisher
American Chemical Society
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesTheoretical and Computational Biophysics Laboratory1. Journal Articles


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