This thesis has demonstrated that ab initio techniques may be usefully applied to the study of biological systems. Only recently, due to the development of efficient numerical techniques and the availability of large computational resources, has it become possible to study systems of genuine interest in biological fields using a first-principles approach. The techniques which have been used for the simulations described within this thesis were outlined in Chapter . These offer efficient scaling of computational cost with system size and their implementation on massively parallel computers gives access to the computational power needed for useful calculations to be performed on biological systems.
In order to analyse the results of the electronic structure calculations within a biological context, a technique for extracting local atomic properties was implemented. The need for this technique arose due to the use of a plane wave basis set to represent the electronic eigenstates in the ab initio methods described in Chapter . The use of a plane wave basis set offers many advantages, but it does not provide a natural way of calculating local properties such as ionic charges and bond populations. Projection of the electronic eigenstates onto a local atomic basis set allows standard population analysis techniques such as Mulliken analysis to be applied. The theory behind the projection and population analysis was described in Chapter and the implementation of these is outlined in Appendix . Applications of these methods to molecular and bulk systems were also described in Chapter in order to demonstrate their use as an analytical tool.
The use of any new methodology must be validated before proceeding to investigate novel problems. This is particularly true of computational methods, which are most sensibly tested on a small system before proceeding to model a large system which requires a large investment of computer time. To this end, the energetics of acetylcholine were studied. This molecule has been widely investigated using other computational approaches and conventional experimental techniques. A description of the computational modeling performed and the results obtained were presented in Chapter . Comparison of the results of this investigation with experimental data indicated that the ab initio calculations accurately describe the energetics of this molecule. This offered the confidence needed in the computational methodology to explore more speculative questions regarding large systems.
The cytochrome P450 superfamily of enzymes are of great importance due to the wide range of physiological processes in which they participate. The addition of ab initio simulations to the arsenal of experimental techniques applied to the study of these enzymes should offer considerable further insight into the mechanism of their action. Chapter described the application of ab initio methods to these enzymes and demonstrated that they accurately reproduce experimental observations of the interaction between a P450 enzyme and ligand molecules. The inhibition of the catalytic reaction by a water molecule, found at the active site of some P450-ligand complexes, was explored. In contrast to existing theories, this indicated that the water molecule was only indirectly responsible for causing the inhibition of the reaction and the mechanism of this effect was identified.