### Session X39: Focus Session: Crystal Growth of and Moderated by Proteins

2:30 PM–5:30 PM, Thursday, March 19, 2009
Room: 411

Chair: Raymond Friddle, Lawrence Livermore National Laboratory

Abstract ID: BAPS.2009.MAR.X39.9

### Abstract: X39.00009 : Atomistic Investigation of Cu-Induced Misfolding in the Onset of Parkinson's Disease

4:54 PM–5:06 PM

MathJax On | Off     Abstract

#### Authors:

Francis Rose
(NCSU)

Miroslav Hodak
(NCSU)

Jerry Bernholc
(NCSU)

A nucleation mechanism for the misfolding of $\alpha$-synuclein, the protein implicated in Parkinson's Disease (PD), is investigated using computer simulations. Through a combination of ab initio and classical simulation techniques, the conformational evolution of copper-ion-initiated misfolding of $\alpha$-synuclein is determined. Based on these investigations and available experimental evidence, an atomistic model detailing the nucleation-initiated pathogenesis of PD is proposed. Once misfolded, the proteins can assemble into fibrils, the primary structural components of the deleterious PD plaques. Our model identifies a process of structural modifications to an initially unfolded $\alpha$-synuclein that results in a partially folded intermediate with a well defined nucleation site as a precursor to the fully misfolded protein. The identified pathway can enable studies of reversal mechanisms and inhibitory agents, potentially leading to the development of effective therapies.

To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2009.MAR.X39.9