A thesis submitted to the Faculty of Science University of the Witwatersrand in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 1998. / Conformational analysis of portions of functionally-active and functionally-inactive signal peptides (incorporating the wild-type and mutants thereof) has been performed using a variety of computational prediction techniques based on both statistics and molecular mechanics. Molecular mechanics conformational studies are generally plagued by the problem of combinatorial explosion; this problem was addressed with a systematic searching procedure as well as a recently developed genetic algorithm, both utilising tile ECEPP/3 force field. The genetic algorithm, in combination with a gradient minimiser, proved to be successful in finding low-energy conformations for each peptide sequence studied. Analysis was performed in both simulated hydrophobic and hydrophilic environments, under distance-constraints. The molecular mechanics results and statistical predictions generated from the study were compared With existing experimental observations. The reliability of statistical predictions proved to be dependent on prediction method; the more consistent predictions were produced by methods based on membrane proteins, as opposed to those based on globular proteins. The physical property of hydrophobicity of signal peptide sequences, explored in these statistical predictions, was determined to be an important factor in relating sequence to functional activity. Molecular mechanics calculations produced either interrupted or non interrupted a-helical secondary structures both for functionally-efficient and for functionally-inefficient signal peptides, indicating that cc-helixformation alone cannot be correlated with protein export competence. It was concluded from our overall results that both a-helicity and hydrophobicity are required for the efficient functioning of signal peptides. / AC2017

Thesis (M.Tech.: Chemistry)-Dept. of Chemistry, Durban Institute of Technology, 2003 ix, 70 leaves + 1 computer laser optical disc / The purpose of this study is to utilize computational techniques in the determination of the mechanistic pathways for the one-pot conversion of a pentacyclo-undecane (PCU) dione 1.1 to a pentacyclo-undecane cage lactam 1.2.

Thesis (M.Tech.: Chemistry)-Dept. of Chemistry, Durban Institute of Technology, 2003 ix, 70 leaves + 1 computer laser optical disc / The purpose of this study is to utilize computational techniques in the determination of the mechanistic pathways for the one-pot conversion of a pentacyclo-undecane (PCU) dione 1.1 to a pentacyclo-undecane cage lactam 1.2.