Chapter 1. Production of crystals for diffraction analysis would be assisted by the devising of a set of rules which, given molecular formula, could predict crystal formation conditions. By studying trends in structural properties of a group of closely related simple molecules, deductions could be drawn which could then be applied more generally. Chalcone derivatives with minor substituent differences were recrystallised. X-ray diffraction data collected and the structures solved and refined. Additionally, NMR and UV studies were performed, investigating an observed dimerisation reaction. Chapter 2. Discovery of peptide hormones and neurotransmitters has stimulated the study of structure-activity relationships, although the structure of these molecules is often poorly defined. Proctolin, a linear pentapeptide, is a neurotransmitter in insects. Crystallisation was attempted, with the aim of deducing the active conformation structure, thereby assisting in design of small molecule analogues for use as non-cholinergic pesticides. No diffraction was observed from the crystals produced. Chapter 3. Glucosamine 6-phosphate synthase is an N-terminal nucleophile amidotransferase catalysing the first step in the hexosamine pathway, from which all amino-sugar containing macromolecules are derived. Structure determination of each of two subdomains was attempted. In one case, pseudo-symmetry appeared to obstruct structure solution. The symmetry has subsequently been understood and the structure obtained. Crystals of the second domain are rotationally disordered. Chapters 4 and 5. Recent advances in macromolecular crystallographic techniques have facilitated the collection of an increasing number of high quality, atomic resolution data sets. Methods for refinement, previously limited to small molecule structures, have increasing relevance for proteins. Atomic resolution refinements using these evolving protocols have been performed on two small proteins, rubredoxin from Desulfovibrio vulgaris and the protein G immunoglobulin-binding domain. Appropriate treatment of the solvent structure in a protein crystal and the benefit to be gained by using sharpened density maps during refinement were investigated.

This work examines the deposition of metallic and semiconductor elements onto self-assembled DNA templates for the fabrication of nanodevices. Biological molecules like DNA can self-assemble into a variety of complex 2-D and 3-D architectures without the need for expensive patterning tools. In addition, self-assembled DNA templates can be designed to controllably place functional nanomaterials with molecular precision. These characteristics make DNA an attractive template for fabricating electronic circuits from biological molecules. However, electrically conductive structures are required for electronic applications. While metallized DNA nanostructures have been demonstrated, the ability to make thin, continuous wires that are electrically conductive still represents a formidable challenge. DNA-templated wires have generally been granular in appearance with a resistivity approximately two to three orders of magnitude higher than that of the bulk material. An improved method for the metallization of DNA origami is examined in this work that addresses these challenges of size, morphology and conductivity of the metallized structure. Specifically, we demonstrated a metallization process that uses gold nanorod seeds followed by anisotropic electroless (autocatalytic) plating to provide improved morphology and greater control of the final metallized width of conducting metal lines. Importantly, growth during electroless deposition occurs preferentially in the length direction at a rate that is approximately four times the growth rate in the width direction, which enables fabrication of narrow, continuous wires. The electrical properties of 49 nanowires with widths ranging from 13 nm to 29 nm were characterized, and resistivity values as low as 8.9 x 10-7 Ω-m were measured, which represent some of the smallest nanowires and the lowest resistivity values reported in the literature. The metallization procedure developed on smaller templates was also successfully applied to metallize bigger DNA templates of tens of micrometers in length. In addition, a polymer-assisted annealing process was discovered to possibly improve the resistivity of DNA metal nanowires. Following metallization of bigger DNA origami structures, controlled placement of gold nanorods on a DNA breadboard (~100 x 100 nm2) to make rectangular, square and T-shaped metallic structures was also demonstrated. For site-specific placement of nanorods to a DNA template, we modified the surface of the gold nanorods with single-stranded DNA. The rods were then attached to DNA templates via complementary base-pairing between the DNA on the nanorods and the attachment strands engineered into the DNA "breadboard" template. Gaps between the nanorods were then filled controllably via anisotropic plating to make 10 nm diameter continuous metallic structures. Finally, controlled placement of metal (gold) - semiconductor (tellurium) materials on a single DNA origami template was demonstrated as another important step toward the fabrication of DNA-based electronic components. The combination of molecularly directed deposition and anisotropic metallization presented in this work represents important progress towards the creation of nanoelectronic devices from self-assembled biological templates.

In this thesis, six small molecules (S-allylcysteine, S-allyl mercaptocysteine, allicin, methyl propyl disulfide, allyl methyl sulfide and dipropylsulfide) that are found in garlic and onion, and are known to be beneficial for human health were studied using molecular mechanics, semi-empirical methods, ab-initio (Restricted Hartree Fock), and density functional theory. Using the same methods, a synthetic pyrethroid pesticide molecule, called cyfluthrin, was also studied. Structural, vibrational and electronic properties of these molecules were found. These theoretical studies could clarify the role of these molecules on human health before they are commercially developed and used. In addition, unfolding dynamics of small peptide sequences (DDATKTFT and its variants) in immunoglobulin G-binding protein G was investigated. Protein folding and unfolding is one of the most important unsolved problems in molecular biology. Because of the large number of atoms involved in protein folding, it is a massive computational problem. The hope is that, one could understand this mechanism with the help of molecular dynamics simulation on small peptides. One of our findings is that the location of the hydrogen bonds is important for the stability of the peptide.