Takako Takeda

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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)
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)
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)
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)
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)
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)
Using all-atom molecular dynamics, we study the temperature-induced dissociation of Abeta monomers from the fibril protofilament. To accelerate conformational sampling, simulations are performed at elevated temperatures and peptide concentrations. By computing free energy disconnectivity graphs we mapped the free energy landscape of monomers on the surface(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)
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)
MOTIVATION Computational modeling of protein-DNA complexes remains a challenging problem in structural bioinformatics. One of the key factors for a successful protein-DNA docking is a potential function that can accurately discriminate the near-native structures from decoy complexes and at the same time make conformational sampling more efficient. Here, we(More)