Protein aggregation is associated with serious and eventually-fatal neurodegenerative diseases including Alzheimer’s , Parkinson’s and the prion diseases. While atomic resolution molecular dynamics simulations have been useful in this regard, they are limited to examination of either oligomer formation by a small number of peptides or analysis of the stability of a moderate number of peptides placed in trial or known experimental structures. We describe large scale molecular dynamics simulations of the spontaneous formation of fibrils by systems containing large numbers of peptides. The simulations are fast enough to enable us to follow the steps in the aggregation process from an initial configuration of random coils to oligomers and then to proto-filaments with cross-β structures. In simulations of Aβ17-42 peptides we uncovered two fibrillization mechanisms that govern their structural conversion from disordered oligomers into protofilaments. We also investigate the influence of crowding agents on oligomerization and fibrillization for Aβ16-22. Simulations are conducted which allow examination of the impact of naturally-derived inhibitors (resveratrol, curcumin, vanillin, and curcumin) on the oligomerization and fibrillation of A β17-36. Finally we describe simulations of human, mouse and Syrian Hamster fragments of the prion protein, PrP(120-144), in effort to understand cross seeding. The results of all of the simulations are compared to experiment. Movies of the aggregation process on a molecular level will be shown.
Professor Carol K. Hall is the Camille Dreyfus Distinguished University Professor of Chemical and Biomolecular Engineering at North Carolina State University. She received her B.A. in physics from Cornell University and her Ph.D. in physics from the State University of New York at Stony Brook. After postdoctoral training in the Chemistry Department at Cornell and a brief period as an economic modeler at Bell Laboratories, she joined the Chemical Engineering Department at Princeton University in 1977 as one of the first women to be appointed to a chemical engineering faculty in the U.S. In 1985 she joined the Chemical Engineering Department at North Carolina State University. Hall’s research focuses on applying statistical thermodynamics and molecular-level computer simulation to topics of chemical, biological or engineering interest involving macromolecules or complex fluids. Current research topics include protein folding/aggregation, multipolar colloids, protein design, amino-acid-based polymers, dispersants for oil spills, liposomal drug delivery devices, and nanoparticle toxicology. She is the author of over 250 publications, is a Fellow of the American Institute of Chemical Engineers and of the American Physical Society and was elected to the National Academy of Engineering in 2005.
About Elizabeth D. Rockwell
A fourth generation Houstonian, Mrs. Rockwell was an Executive Director, Private Client Division of CIBC Oppenheimer Corp. She was widely recognized as an expert in retirement, estate, investment, and tax planning. She was an early proponent of the Keogh and IRA plans, for which she has been nationally recognized.
In 1991, she qualified to be a member of the Million Dollar Round Table as well as the Texas Leaders Round Table. Since 1990 she had authored a monthly column for the Houston Chronicle.
Mrs. Rockwell served as President of the UH College of Business Administration Foundation Board, as a member of the Dean’s Advisory Board, and was an Executive Professor for the college. She also served as a member of the advisory board of the Health Law and Policy Institute and as a Trustee of the University of Houston System’s Foundation, as well as a member of the UH System’s Planned Giving Council.
Mrs. Rockwell served on the Board of Governors for the Houston Forum, and as a Board member of the American Red Cross, the Greater Houston Women’s Foundation, the University of Houston Alumni Organization, and the Greater Houston Preservation Alliance. She was a member of the River Oaks Business Women’s Exchange Club, the National Tax Sheltered Annuity Association, the Texas Association of College Teachers, and the Houston Association of Life Underwriters.
Among her numerous honors, she has received an Honorary Doctorate of Humane Letters from the University of Houston, the Distinguished Alumna Award from the Houston Alumni Organization and from the UH College of Business Administration. Throughout the years she has been recognized for her many achievements by the Education Foundation of Harris County, the Houston Community College System’s Television Station Advisory Council, and the Houston Mayor’s READ Commission.
The Houston Alumni Center is home to the Elizabeth D. Rockwell President’s Suite. In September 1997, the Elizabeth D. Rockwell Career Services Center was opened in the UH College of Business Administration. She endowed the Chair for the Dean of the M.D. Anderson Library.
Mrs. Rockwell was listed in the Who’s Who in the South and Southwest; Who’s Who in finance and Industry; Who’s Who of American Women; and Who’s Who in the World.