Discrete Molecular Dynamics Study of wild-type and Arctic-mutant (E22G) Aβ16−22 Folding and Aggregation
Substantial clinical and experimental evidence supports the hypothesis that amyloid β-protein (Aβ) forms assemblies with potent neurotoxic properties that cause Alzheimer’s disease (AD). Therapeutic targeting of these assemblies would be facilitated by the elucidation of the structural dynamics of A...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Text |
| Language: | English |
| Published: |
2008
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| Subjects: | |
| Online Access: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.378.9575 http://cps-www.bu.edu/hes/articles/ypcbtsu08.pdf |
| Summary: | Substantial clinical and experimental evidence supports the hypothesis that amyloid β-protein (Aβ) forms assemblies with potent neurotoxic properties that cause Alzheimer’s disease (AD). Therapeutic targeting of these assemblies would be facilitated by the elucidation of the structural dynamics of Aβ aggregation at atomic resolution. We apply the ab initio discrete molecular dynamics approach coupled with a four-bead peptide model to study the aggregation of wild-type and Arctic-mutant (E22G) Aβ16−22, a peptide that contains the Aβ central hydrophobic cluster, Leu17–Ala21, that plays an important role in Aβ assembly. The aggregation of sixteen wild-type Aβ16−22 peptides is studied systematically under solvent conditions incorporating: (i) effective hydropathic and electrostatic interactions; (ii) no effective hydropathic interactions; and (iii) no effective electrostatic interactions. We find that at physiological temperatures initially-separated peptides aggregate into fibrillar units under condition (i). These units comprise multi-layered |
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