All-Atom Explicit-Solvent Replica-Exchange Molecular Dynamics Simulations of the Alzheimer’s Disease Aβ Monomer

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dc.contributor.advisorKlimov, Dmitri
dc.contributor.authorLockhart, Christopher
dc.creatorLockhart, Christopher
dc.date.accessioned2016-04-19T19:28:47Z
dc.date.available2016-04-19T19:28:47Z
dc.date.issued2015
dc.description.abstractUsing all-atom explicit-solvent replica-exchange molecular dynamics simulations, we explored the changes in the conformational ensemble of the Aβ monomer in various environments. In the simplest case, the Aβ monomer in water forms mostly turn and random coil conformations. We show that the anti-aggregation agent ibuprofen, the zwitterionic DMPC lipid bilayer, and even the introduction of sequence truncation (to generate the Aβ29-40 monomer) are capable of dramatically altering Aβ conformations, resulting in a stable helical structure present in the peptide’s C-terminal. For comparison, the FDDNP biomarker and other sequence truncations (e.g., the Aβ23-40 and Aβ28-40 monomers) do not exhibit a strong influence on Aβ conformations. Thus, we conclude that there is an inherent helix propensity in the Aβ C-terminal that can only be revealed by certain environments.
dc.format.extent194 pages
dc.identifier.urihttps://hdl.handle.net/1920/10166
dc.language.isoen
dc.rightsCopyright 2015 Christopher Lockhart
dc.subjectBiophysics
dc.subjectAlzheimer's disease
dc.subjectAβ peptide
dc.subjectDMPC bilayer
dc.subjectFDDNP
dc.subjectIbuprofen
dc.subjectMolecular dynamics
dc.titleAll-Atom Explicit-Solvent Replica-Exchange Molecular Dynamics Simulations of the Alzheimer’s Disease Aβ Monomer
dc.typeDissertation
thesis.degree.disciplineBioinformatics and Computational Biology
thesis.degree.grantorGeorge Mason University
thesis.degree.levelDoctoral

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