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Introduction

Living organisms are the product of a complex interplay of cellular processes. These processes are controlled through the interactions of molecules within and between cells. Much progress has been made in understanding the details of these phenomena through basic research in many areas of experimental biology. Yet our understanding of biological systems as a whole is largely superficial. The parallel, interconnected and apparently redundant nature of many processes renders them intractable to dissection by standard techniques. The field known as `integrative biology' has been born out of the need to assimilate information from diverse fields and formulate more complete theories to explain the living world.

Computational biology will have a central role in this field because of the ease with which computers can handle large amounts of data and probe the non-linear dynamics of nature. The experimental determination of macromolecular structures has helped to unravel the mysteries of many cellular processes. Three dimensional structure, intermolecular interactions and function are closely linked. Unfortunately, the networks of interactions between molecules in vivo do not always fit the simple models we are often forced to assume. Computer simulation of complex systems like these is possibly the only route towards determining their behaviour. This approach will require a deeper understanding of interactions between biological molecules, and faster routes to the determination of their structures.

The majority of the complex cellular machinery is protein. Other components, such as nucleic acid, carbohydrate and lipid, also play important roles, however proteins perform the widest array of functions throughout the cell and beyond. Genome sequencing projects around the world[Fleischmann et al., 1995,Fraser et al., 1995,Bult et al., 1996, for example] are rapidly collecting genetic information from a number of organisms. The genome completely specifies the construction and maintenance of an organism primarily through the encoding of its proteins, collectively known as the proteome. Consequently, biochemists are faced with the task of translating genome and proteome into a functional description of cells and organisms. The work described in this thesis is part of this effort to break the code.