REPORTS & PUBLICATIONS
Listed below are a selection of the reports and
publications I have written that are currently available online. See my
research page for details of papers I have
recently published and conference presentations.
1) Ph.D. Thesis - "The Development of a QM/MM Based
Linear Response Method and its Application to Proteins"
Abstract: The equilibrium dynamics of a
protein are of fundamental importance in understanding the relationship
between its function and structure. Electronic structure calculations
employing the CIS method for calculating excited states have been coupled
with MD simulations to track the fluctuations in the ground to excited
state energy of LADH as a function of time. Through the use of a QM/MM
framework for predicting optical spectra based on linear response theory
the UV/VIS absorption and emission spectra for NADH in LADH have been
calculated yielding a Stokes shift prediction that is within 13 % of
experiment and widths that are within 1.2 %. The Stokes shift would appear
to be produced from intramolecular interactions on a timescale of around 6
to 8 fs. The spectral widths are sensitive to the amplitude and time scale
of the protein fluctuations, while the Stokes shift is a direct measure of
the extent of relaxation of the molecular system. Accurate reproduction of
these properties acts as an indicator of the performance of the
methodology for probing equilibrium fluctuations and the large Stokes
shift of NADH tests the limit of the linear response assumption. The
quality of the results very much depend on the quality of the MD
trajectory used and as such the method provides a way to validate MD force
field parameters for chromophores via direct comparison with experiment.
The results demonstrate that an extension of the QM/MM
approach to the calculation of free energy surfaces is a viable objective
even for very large and very fast fluctuations in systems as complex as
proteins.
Simulations using semi-empirical and TD-DFT evaluation of the
energy gap fluctuations have cast doubt on the ability of such methods to
accurately evaluate the energy gap fluctuations of equilibrium structures.
Extension of the method to zinc-myoglobin has uncovered the
existence of correlation between two degenerate excitations. Work is
currently in progress to use these results to predict anisotropy
experiments.
The thesis is available for download in Adobe PDF format
via the following link.
Ross_Walker_Thesis_Final.pdf
(26,871 KB)
Supplementary Material CD-ROM -
ISO FILE (29,848
KB)
Please cite this work as:- 'Walker, R.C. "The
Development of a QM/MM Based Linear Response Method and its Application
to Proteins", Ph.D. Thesis, Imperial College London,
London Oct 2003'
2) Ph.D. Transfer Report - "Calculations of Optical
Spectra of LADH via Application of Linear Response Theory"
Abstract: A common misconception in
chemistry is to consider systems to be static in nature. We are very used
to building a static picture of systems: X-ray structures; ball- and
stick- models; optimised geometries etc. The dynamics of a protein,
however, are very important to its reactivity and its structure alone is
not sufficient to predict its function. Here CIS electronic structure
calculations have been employed to derive the fluctuation in the ground to
excited state energy gap of dihydro-Nicotinamide Adenine Dinucleotide
(NADH) embedded in the Horse Liver Alcohol Dehydrogenase (LADH) protein
matrix as a function of time. Classical molecular dynamics trajectories of
130 ps in length have been run on an LADH+NADH dimer in water to elucidate
the dynamics of equilibrated LADH over a 10 ps timescale. These structures
have then been incorporated within the hybrid Quantum Mechanical/Molecular
Mechanical (QM/MM) protocol for single point CIS calculations.
Steady-state absorption and emission spectra have then been produced for
comparison with experiment within a framework, utilising linear response
theory. It has been found that the accuracy of the results obtained is
very dependent on the quality of the molecular dynamics trajectory,
especially in the parameterisation of the nicotinamide moiety. The results
have successfully shown that linear response theory can work for systems,
such as NADH, which have very large reorganisation energies yielding
predicted spectra that are within 13 % of experiment.
The report is available for download in Adobe PDF format
via the following link.
NOT CURRENTLY AVAILABLE
Please cite this work as:- 'Walker, R.C. "Ph.D.
Transfer", Imperial College of Science, Technology and
Medicine, 2001'
3) 4th Year Research Project - "An Investigation
of the Reactivity of Myoglobin Using Quantum Mechanical Techniques."
This report is the writeup of my 4th year chemistry MSci
research project carried out during 1999/2000 in the Gould group at
Imperial College. The project was concerned with using quantum
chemistry techniques to investigate the mechanism by which myoglobin
(the oxygen storage protein found in mammalian muscle) actively discriminates
between carbon monoxide and oxygen as potential ligands for binding to
the iron atom of the heme unit active site.
The report is available for download in Adobe PDF format
via the following link.
4th_year_project.pdf
(2618 KB)
Project_CDROM.rar
(63719 KB)
Please cite this work as:- 'Walker, R.C. "4th Year
Research Project", Imperial College of Science, Technology and
Medicine, 2000'
4) 3rd Year Technical Literature Report -
"Multipole Methods for Solving Electronic Wavefunctions - A Method for
Achieving Linear Scaling in Electronic Structure Calculations."
This report is my 3rd year technical literature report
that was submitted in partial fulfilment of the course work component
for the 3rd year of my MSci degree at Imperial College. The report
is a summary of the theory involved and recent developments in the field
along with suggestions of the paths future research is likely to take.
The report is available for download in Adobe PDF format
via the following link.
3rd_year_lit_report.pdf
(1560 KB)
Please cite this work as:- 'Walker, R.C. "3rd Year
Literature Report", Imperial College of Science, Technology and
Medicine, 2000'
5) Website on the History, Medicinal Properties
and Artificial Synthesis of the Anti Cancer Drug Paclitaxel (Taxoltm)
This website was developed as part of the coursework
requirement for the second year MSci chemistry IT course at Imperial
College and is included here as a general source of information on the
anti cancer drug Taxol.
The pages are available via the following link.
http://www.rosswalker.co.uk/taxol/
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