Date of Award

Fall 2004

Document Type


Degree Name

Doctor of Philosophy (PhD)


Computational Analysis and Modeling

First Advisor

Don Haynie


The focus of this research is the development of computational approaches to understanding the physical basis of layer-by-layer assembly (LBL), a key methodology of nanomanufacturing. The results provided detailed information on structure which cannot be obtained directly by experiments.

The model systems chosen for study are polypeptide chains. Reasons for this are that polypeptides are no less polyelectrolytes than the more usual polyions, and one can control the primary structure of a polypeptide on a residue-by-residue basis using modern synthetic methods. Moreover, as peptides constitute one of the four major classes of biological macromolecules, research in this direction is expected to advance development of bionanotechnology. Polypeptide thin films are a type of new material, and there is great potential for applications in biocompatible implants, drug delivery, and other areas.

A key consideration in polypeptide design for LBL is charge properties as a function of pH. This work presents a computational approach to identify structural motifs in amino acid sequence data and to minimize the immune response to polypeptides based on the structural motifs and demonstrate by experiments.

This work also presents innovative molecular dynamics (MD) work on LBL. All-atom models have been used to investigate polypeptide LBL at the sub-molecular level. The peptide structures studied—homopolymers of lysine and of glutamic acid, and designed cysteine-containing peptides—correspond to ones for which experimental data have been obtained in the Haynie research laboratory. Simulations were carried out to study structural and dynamical properties of peptide models having some combination of parallel and anti-parallel β sheets, as such structures are known to be formed by the indicated peptides in LBL films.

The MD work suggests that hydrophobic interactions too play an important role in polypeptide LBL. Moreover, hydrogen bonding appears to be a consequence of polypeptide LBL instead of a major driving force for stabilizing secondary structures in polypeptide multilayer thin films. Results of simulations of 6-residue and 8-residue peptides further suggest that if the shorter peptides can form a stable superstructure in the vicinity of 350 K, the most likely conformation will be anti-parallel β strands within a layer and parallel β strands between layers.