It's over
On 19 Jul 2006, I submitted the final archival copy of my thesis to the RMIT Higher Degrees unit, which marked the end of my student life. The thesis was subsequently entered into the Australasian Digital Theses Program, which allows anyone to download my thesis.
Abstract
The use of electromagnetic devices such as microwave ovens and mobile phones has certainly brought convenience to our lives. At the same time, the proliferation of said devices has increased public awareness of the potential health hazards. It is generally assumed that there is little or no risk associated with the use of electromagnetic devices, based on the small amount of power associated with those devices. However, case studies on animals indicate that the risk cannot be entirely ruled out.
It has long been known that proteins are sensitive to stress, arising from various sources such as temperature, chemical, pressure, and changes in pH condition. In all of these cases, the protein exhibits clear signs of damage and distress, which range from slight unfolding to complete loss of structure. Frequently, the damage to the protein is alleviated by refolding, either by itself or by the aid of molecular chaperones. However, if the damage to the protein is too great, the protein will generally undergo proteolysis.
Opinion has been divided over the implication of prolonged use of electromagnetic devices to human health. Studies conducted on animals so far have given conflicting results. The studies on the separate components, electric and magnetic fields, also give inconclusive results. This indicates that our understanding on how electric and magnetic fields interact with biological matter is incomplete.
In this project, we use molecular dynamics to explore the behaviour of two forms of insulin chain-B, isolated and monomeric (in the presence of chain-A with all disulfide bonds intact), at ambient conditions and under the influence of various stress. Specifically, we focus our attention to thermal stress and electric field stress. The electric field stress considered in this study takes several forms: static and oscillating with three different frequencies. These fields have strength ranging from 1806 V/m to 109 V/m.
By performing molecular dynamics simulations totalling over 500 ns, we have gained valuable insights into the effects of elevated temperature and electric field on insulin chain-B. We observed differences in the damage mechanisms by the application of static electric field and oscillating field. The application of static fields restricts the conformational freedom of a protein, whereas the application of oscillating fields increases the mobility and flexibility of the protein, similar to the effect of thermal stress. Both of these interfere with the normal behaviour of a protein. We have also observed frequency-dependent effects, with low frequency fields having static field-like characteristics in damage mechanism.
List of resulting publication
- Peer-reviewed publications
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Comparative Study of Insulin Chain-B in Isolated and Monomeric Environments under External Stress" J. Phys. Chem. B, 112(26):7916-7924 (2008)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Effect of Frequency on Insulin Response to Electric Field Stress" J. Phys. Chem. B, 111(20):5748-5756 (2007)
- F.S. Legge, A. Budi, H. Treutlein, I. Yarovsky, "Protein Flexibility: Multiple Molecular Dynamics Simulations of Insulin Chain B" Biophys. Chem., 119(2):146-157 (2006)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Electric Field Effects on Insulin Chain-B Conformation" J. Phys. Chem. B, 109(47):22641-22648 (2005)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Protein Response to Electric Field Stress" Proceedings of the 16th Australian Institute of Physics Congress 2005 Canberra, Australia (2005) ISBN 0-9598064-8-2
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Effect of External Stresses on Protein Conformation: A Computer Modelling Study" Eur. Biophys. J., 33(2):121-129 (2004)
- Conferences papers/publications
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "On The Effects of Stresses on Protein Conformation" Molecular Modelling 2007, Melbourne, Australia (2007)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "On The Effects of Stresses on Protein Conformation" Workshop: Interaction Energies and the Structure of Surfaces and Nano-structures, Melbourne, Australia (2007)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Protein Misfolding Due to External Stress: A Theoretical Study" 10th Molecular Modelling Workshop, Perth, Australia (2006)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Protein Response to Electric Field Stress" 31th Annual Lorne Conference on Protein Structure and Function, Lorne, Australia (2006)
- F.S. Legge, A. Budi, H. Treutlein, I. Yarovsky, "Protein Flexibility: Multiple Molecular Dynamics Simulations of Insulin Chain B" 30th Annual Lorne Conference on Protein Structure and Function, Phillip Island, Australia (2005)
- F.S. Legge, A. Budi, H. Treutlein, I. Yarovsky, "Protein Flexibility: Multiple Molecular Dynamics Simulations of Insulin Chain B" Biomolecular Dynamics and Interactions Symposium, Melbourne, Australia (2005)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Computer Simulation Study of Electric Field and Temperature Effects on Insulin Chain B" 29th Annual Lorne Conference on Protein Structure and Function, Lorne, Australia (2004)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Detailed Structural Analysis of the Transition Pathway of Stressed Insulin Using the Conformational Analysis Tool PEPCAT" 28th Annual Lorne Conference on Protein Structure and Function, Lorne, Australia (2003)
- A. Budi, F.S. Legge, H. Treutlein, I. Yarovsky, "Unfolding Pathways of Chemically and Thermally Stressed Insulin: A Molecular Dynamics Study" Bioactive Discovery in the new millenium, International Modelling conference, Lorne, Australia (2003)
- Y. Berry, A. Budi, J. Carver, H. Treutlein, I. Yarovsky, "Response of Proteins to External Non-Ionising Radiation: An Experimental and Computer Modelling Investigation" The 26th Annual Conference of the Australian Society for Biophysics, Melbourne, Australia (2002)
PhD citation
Dr Budi examined the effects of different stresses, such as thermal, chemical and electric field on the behaviour of the insulin chain-B in two forms: isolated, and as part of an insulin monomer. Utilising molecular dynamics simulations, he systematically explored the atomistic mechanisms of interaction within the insulin chain-B under these different stresses. The research highlighted the different damage mechanisms that can occur from each of the stresses and this advances the understanding of how proteins respond under stress