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Folding and self-assembly of polypep...

Fluitt, Aaron Michael.

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Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation./
作者:	Fluitt, Aaron Michael.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2015,
面頁冊數:	157 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.
Contained By:	Dissertation Abstracts International77-02B(E).
標題:	Biophysics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3724466
ISBN:	9781339079769

Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation.
Fluitt, Aaron Michael.

Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation. - Ann Arbor : ProQuest Dissertations & Theses, 2015 - 157 p.

Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.

Thesis (Ph.D.)--The University of Chicago, 2015.

Empowered by their exquisite three-dimensional structures, or "folds," proteins carry out biological tasks with high specificity, efficiency, and fidelity. The fold that optimizes biological function represents a stable configuration of the constituent polypeptide molecule(s) under physiological conditions. Proteins and polypeptides are not static, however: battered by thermal motion, they explore a distribution of folds that is determined by the sequence of amino acids, the presence and identity of other molecules, and the thermodynamic conditions. In this dissertation, we apply molecular simulation techniques to the study of two polypeptides that have unusually diffuse distributions of folds under physiological conditions: polyglutamine (polyQ) and islet amyloid polypeptide (IAPP). Neither polyQ nor IAPP adopts a predominant fold in dilute aqueous solution, but at sufficient concentrations, both are prone to self-assemble into stable, periodic, and highly regular aggregate structures known as amyloid. The appearance of amyloid deposits of polyQ in the brain, and of IAPP in the pancreas, are associated with Huntington's disease and type 2 diabetes, respectively. A molecular view of the mechanism(s) by which polyQ and IAPP fold and self-assemble will enhance our understanding of disease pathogenesis, and it has the potential to accelerate the development of therapeutics that target early-stage aggregates. Using molecular simulations with spatial and temporal resolution on the atomic scale, we present analyses of the structural distributions of polyQ and IAPP under various conditions, both in and out of equilibrium. In particular, we examine amyloid fibers of polyQ, the IAPP dimer in solution, and single IAPP fragments at a lipid bilayer. We also benchmark the molecular models, or "force fields," available for such studies, and we introduce a novel simulation algorithm.

ISBN: 9781339079769Subjects--Topical Terms:

518360
Biophysics.

Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation.
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