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.