Computational studies of tau protein : implications for the pathogenesis and treatment of neurodegenerative diseases

Tau protein is the primary constituent of protein aggregates known as neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). Previous studies suggest that tau protein may play a contributing role in neurodegenerative diseases such as AD. Thus characterizing the structural properties of tau is critical to understanding disease pathogenesis. However, obtaining a detailed structural description of tau protein has been difficult because it belongs to a class of heteropolymers known as intrinsically disordered proteins (IDPs). Unlike most proteins, IDPs adopt many distinct conformations under physiological conditions. In spite of their disordered nature, evidence exists that such proteins may exhibit residual structural preferences. In this work, models of tau are constructed to characterize these structural preferences. We begin by performing molecular dynamics simulations to study the inherent conformational preferences of the minimal tau subsequence required for in vitro aggregation. To model residual structure in larger regions of tau, we developed a novel method called Energy-minima Mapping and Weighting (EMW). The method samples energetically favorable

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Huang, Austin V., 1980-

Advisor dc:contributor.advisor

• Collin M. Stultz.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/54453

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/54453