Use this URL to cite or link to this record in EThOS:
Title: Computational modelling of the reduction of heavy metals by cytochromes
Author: Campbell, Andrew James
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2006
Availability of Full Text:
Access from EThOS:
One of the most important areas of scientific interest is the clean up and prevention of pollution. The work discussed in this thesis investigates a method that could be potentially used in the future to control and manage a variety of highly toxic heavy metals. This thesis is an attempt to study the reduction of toxic heavy metals by cytochrome C7 from the bacteria Desulfuromonas acetoxidans using quantum mechanical methods. The study started systematically by identifying numerous chromate and uranyl binding sites on the surface of the cytochrome using a genetic algorithm search program, Autodock (see Chapter 4). The sites found were further analysed using density functional theory (DFT) by calculating the binding energies of the metal bound ligands and further using the empirical HARLEM program to analyse the donor-to-acceptor electronic coupling. We have studied the structure and redox properties of the three hemes present in the cytochrome C7. as their reduction potentials are important in determining the rate of electron transfer to enhance the understanding into the mechanism for heavy metal reduction. We here describe computational studies of cytochrome C7 designed to define more accurately the geometric structures of the three heme active sites in their reduced and oxidised states, and thus understand how these structures determine the redox potentials of these proteins (see Chapter 5). Two level ONIOM calculations involving DFT and molecular mechanical potentials are used to predict both the geometric and electronic structure of the three heme active sites. These studies identify the critical role of the propionate side chains and the surrounding protein residues have in tuning the redox potentials of the three hemes. We have used cost effective PM3 method using the new developed semi-empirical parameters for iron and tested with and without the protein back bone. The usefulness of these parameters are highly encouraging and may be used in the future to study the dynamics of the protein at the quantum mechanical level. In chapter 6, we have studied the structure and redox properties of both metal (Mn, Ni, and Co) and ligand (cysteine and methionine) mutations of the heme active site which are highly useful in tuning the reorganization energies and redox potentials, which are central in determining the rate of electron transfer. We have described the geometric changes that occur at the heme site and by the bound chromate using DFT methods (Chapter 7). We have concluded that protonation and solvation of the chromate is a key process in determining the electron transfer from the heme to the heavy metal chromate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available