*Dissertation Defense Announcement:
To:  The George Mason University Community*

*Wenling Eileen Chang
PhD Bioinformatics & Computational Biology Candidate
*
*Date:   Thursday April 28, 2011
Time:   11:00 a.m. 
Place:  George Mason University
** 	     Occoquan Bldg. Room 203
	     Prince William campus <http://www.gmu.edu/resources/visitors/findex.html>
  
Dissertation Chair: Dr. Dmitri Klimov
Committee members: Dr. Saleet Jafri, Dr. Iosif Vaisman, Dr. Estele Blaisten-Barojas*

*Title: "Computational Modeling of Anti-Aggregation Effect of Non-Steroidal
           Anti-Inflammatory Drugs in Alzheimer's Amyloidogenesis"****
*
The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
The doctoral project will not be read at the meeting, but should be read in advance. 
/**/
*All members of the George Mason University community are invited to attend.
*

*ABSTRACT:*

Alzheimer's disease (AD) represents a growing biomedical, social, and 
economical problem. Studies have shown that aggregated forms of amyloid 
? peptide adversely affect neuronal function and may represent the 
causative agent in AD. It has been demonstrated that chronic treatment 
with ibuprofen and naproxen reduces the risk of AD and improves the 
behavioral impairment for patients with AD. This dissertation utilizes 
high performance parallel computing, all-atom molecular dynamics 
simulation, and protein-ligand docking to understand the mechanism of 
the anti-aggregation effect of ibuprofen and naproxen in Alzheimer's 
amyloidogenesis. The results reveal different mechanisms of ligand 
binding to the monomers and fibrils formed by A? peptides implicated in 
AD.  Binding to A? monomers is mostly governed by ligand-amino acid 
interactions, whereas binding to the fibril is determined by the fibril 
surface geometry and interligand interactions. The anti-aggregation 
effect of ibuprofen and naproxen is explained by direct competition 
between these ligands and incoming A? peptides for binding to the fibril.  

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