Self-Assembly in Biological Systems Explored Through Multi-Scale Modeling Methods

Friday, April 3, 2009 - 10:00 p.m. to Saturday, April 4, 2009 - 10:55 p.m.
ChEMS Seminar

Featuring Hung D. Nguyen, Ph.D.
Postdoctoral researcher
Department of Chemistry and Biophysics Program
University of Michigan

Location: McDonnell Douglas Engineering Auditorium
Free and open to the public

Abstract:
Self-assembly is the autonomous organization of simple components into complicated and interesting patterns or structures at all scales and are common throughout nature and technology. In this seminar, I will discuss two studies of self-assembly by proteins at nanoscale via multi-scale modeling methods.

The first study concerns the competition between protein folding and aggregation, which is a serious problem in the biotechnology and pharmaceutical industries since protein aggregation can interfere with the stability of protein-based drugs. I will focus on the formation of ordered structures such as amyloid fibrils, which have been implicated in the pathology of several neurodegenerative diseases including Alzheimer's and Parkinson's. I will present molecular-level results from large simulations on systems containing hundreds of polyalanine peptides, each containing 16 residues which are represented in adequate detail by our simplified protein model. This novel model is simple enough to allow the simulation of multi-protein systems over relatively long time scales, yet contains enough genuine protein-like character to mimic real protein dynamics. Polyalanine was chosen for study because synthetic polyalanine-based peptides, which form -helical structures at low temperatures and low peptide concentrations, have been found to form -sheet complexes (fibrils) in vitro at high temperatures and high peptide concentrations. Although our works were purely computational, the results obtained from our simulations have been validated by various experimental and computational groups.

The second study examines the self-assembly of viral capsids, which are spherical shells that envelop and protect the viral genome and are composed of multiple copies of the same protein. In order to propagate an infection, the capsid proteins must self-assemble correctly, rapidly, and reproducibly on a biological timescale. Elucidating this assembly process of viral capsid formation has significant potential for many beneficial applications in medicine and nanotechnology. Not only can our simulations replicate the scope and morphology of assembled structures that have been observed in experiments, we are also able to elucidate the kinetics and thermodynamics of viral capsid assembly in detail. Emerging from our studies is a new understanding of the kinetic mechanisms responsible for assembling not only canonical capsids but also misdirected structures which are often encountered in in-vitro experiments and vaccine development. These insights can be exploited for the control of assembly products and the improvement of laboratory and manufacturing yields.

About the Speaker:
Hung D. Nguyen is a postdoctoral researcher working with Professor Charles L. Brooks, III, in computational chemistry and biophysics at the Scripps Research Institute in La Jolla, and most recently at the University of Michigan in Ann Arbor. He received his B.S. degree in chemical engineering from the University of Florida. He did his Ph.D. dissertation on "Computer Simulations of Protein Folding and Aggregation" under the guidance of Professor Carol K Hall in chemical and biomolecular engineering at North Carolina State University.