Takako Takeda

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Using replica exchange molecular dynamics simulations and the implicit solvent model we probed binding of ibuprofen to Abeta(10-40) monomers and amyloid fibrils. We found that the concave (CV) fibril edge has significantly higher binding affinity for ibuprofen than the convex edge. Furthermore, binding of ibuprofen to Abeta monomers, as compared to fibrils,(More)
Replica exchange molecular dynamics and all-atom implicit solvent model are used to compute the structural propensities in Abeta monomers, dimers, and Abeta peptides bound to the edge of amyloid fibril. These systems represent, on an approximate level, different stages in Abeta aggregation. Abeta monomers are shown to form helical structure in the(More)
Although the oligomers formed by Aβ peptides appear to be the primary cytotoxic species in Alzheimer's disease, detailed information about their structures appears to be lacking. In this article, we use exhaustive replica exchange molecular dynamics and an implicit solvent united-atom model to study the structural properties of Aβ monomers, dimers, and(More)
Nonsteroidal anti-inflammatory drugs are considered as potential therapeutic agents against Alzheimer's disease. Using replica exchange molecular dynamics and atomistic implicit solvent model, we studied the mechanisms of binding of naproxen and ibuprofen to the Abeta fibril derived from solid-state NMR measurements. The binding temperature of naproxen is(More)
The mechanisms of deposition and dissociation are implicated in the assembly of amyloid fibrils. To investigate the kinetics of unbinding of Abeta(16-22) monomers from preformed fibrils, we use molecular dynamics (MD) simulations and the structures for Abeta(16-22) amyloid fibrils. Consistent with experimental studies, the dissociation of Abeta(16-22)(More)
In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: Using the experimental structures of Aβ amyloid fibrils and all-atom molecular(More)
Replica exchange molecular dynamics and an all-atom implicit solvent model are used to probe the thermodynamics of deposition of Alzheimer's Abeta monomers on preformed amyloid fibrils. Consistent with the experiments, two deposition stages have been identified. The docking stage occurs over a wide temperature range, starting with the formation of the first(More)
Protein-DNA docking is a very challenging problem in structural bioinformatics and has important implications in a number of applications, such as structure-based prediction of transcription factor binding sites and rational drug design. Protein-DNA docking is very computational demanding due to the high cost of energy calculation and the statistical nature(More)
Using replica exchange molecular dynamics, we study the effect of Asp23Tyr mutation on Abeta(10-40) fibril growth. The effect of this mutation is revealed through the computation of free energy landscapes, the distributions of peptide-fibril interactions, and by comparison with the wild-type Abeta(10-40) peptide. Asp23Tyr mutation has a relatively minor(More)
Using replica exchange molecular dynamics simulations and an all-atom implicit solvent model, we probed the energetics of Abeta(10-40) fibril growth. The analysis of the interactions between incoming Abeta peptides and the fibril led us to two conclusions. First, considerable variations in fibril binding propensities are observed along the Abeta sequence.(More)