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 (Taxol^tm)

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/