Dissertation
Influence of aqueous-salt conditions on the structure and dynamics of the monomeric and novel dimeric forms of the Alzheimer's A[beta]21-30 protein fragment
Doctor of Philosophy (Ph.D.), Drexel University
03 Jun 2014
DOI:
https://doi.org/10.17918/etd-4569
Abstract
The behavior of the Alzheimer's related peptide A[beta] is the subject of much study. In typical computational studies the environment local to the peptide is assumed to be pure water; however, in vivo the peptide is found in the extracellular space near the plasma membrane which is rich in ionic species. In this thesis, the hypothesis that the presence of group I/IIA salts will result in increased sampling of disordered structures as well as modify the dynamics of meta-stable structural motifs in the small folding nucleus of the A[beta] peptide (A[beta]_[21-30]) is examined under a variety of ionic environments and was shown that of the tested salts, CaCl₂ (and MgCl₂, to a much lesser degree) did increase the propensity for disordered states; while, the group IA salts, KCl and NaCl, had little effect on the secondary structure of the peptide. Further, study of three familial mutations of this peptide region is also performed under aqueous salt-environments to elucidate further mechanistic details of how aqueous salts modify the region's behavior. Finally, as experimental results have highlighted that aggregation rates of the full-length peptide are modified by the presence of CaCl₂, this work examines novel dimers states of A[beta]_[21-30] and their stabilities when exposed to CaCl₂.
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Details
- Title
- Influence of aqueous-salt conditions on the structure and dynamics of the monomeric and novel dimeric forms of the Alzheimer's A[beta]21-30 protein fragment
- Creators
- Micholas Dean Smith - DU
- Contributors
- Luis R. Cruz Cruz (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Physics; Drexel University
- Other Identifier
- 4569; 991014632074204721