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Dmitri Klimov Department of Bioinformatics and Computational Biology, George Mason University We use all-atom molecular dynamics to study the temperature induced dissociation of Alzheimer’s Abeta monomers from amyloid fibrils. By computing free energy disconnectivity graphs we mapped the free energy landscape of monomers on the surface of Abeta fibril. Abeta peptides sample diverse low free energy states with different degrees of association with the fibril. Some of these states have residual amount of fibril interactions, whereas others lack fibril-like content. Generally, Abeta monomers with partially formed fibril-like interactions have the lowest free energies, but their backbone conformations may differ considerably from those peptides buried in the fibril interior. Overall, Abeta amyloid protofilaments appear to be highly resistant to thermal dissociation. The simulation findings are discussed in the context of recent experimental results.
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