Synthetic and theoretical studies of metal complexes containing carbon-rich ligands. Previous studies in my group, in conjunction with synthetic and theoretical chemistry groups at the Université de Rennes 1, France, have delineated the properties of a series of complexes containing carbon chains linking two metal centres. Having achieved a partial understanding of the features which result in good electronic communication between the metal centres via the carbon chain, the present proposal see ....Synthetic and theoretical studies of metal complexes containing carbon-rich ligands. Previous studies in my group, in conjunction with synthetic and theoretical chemistry groups at the Université de Rennes 1, France, have delineated the properties of a series of complexes containing carbon chains linking two metal centres. Having achieved a partial understanding of the features which result in good electronic communication between the metal centres via the carbon chain, the present proposal seeks to extend this collaboration to further studies which will generate related compounds in which actual eletron exchange can occur, i.e. leading to oxidation/reduction, by using compounds in which two or more different metal centres are present. This may lead to development of nano devices, e.g. molecular-scale switches. If one of the centres is activated by light, a photo-active sensor may result.Read moreRead less
The formation of negative ions and neutrals in the gas phase. Structure, reactivity and mechanism. Mass spectrometry is an analytical technique used to provide information concerning the structure of a chemical compound: it is particularly useful when dealing with small amounts of biologically important molecules. It is also a facility in which charged species can be converted into transient neutrals. This project will (i) produce information about negative ion fragmentations in order to extend ....The formation of negative ions and neutrals in the gas phase. Structure, reactivity and mechanism. Mass spectrometry is an analytical technique used to provide information concerning the structure of a chemical compound: it is particularly useful when dealing with small amounts of biologically important molecules. It is also a facility in which charged species can be converted into transient neutrals. This project will (i) produce information about negative ion fragmentations in order to extend the applicability of analytical negative-ion mass spectrometry, (ii) form neutral molecules and related species which are found in stellar dust clouds and investigate their chemistry, and (iii) train graduates in ion chemistry to the highest international standards.Read moreRead less
From structures to systems: A hierachical approach to understanding sub-cellular components. This program will dramatically extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Au ....From structures to systems: A hierachical approach to understanding sub-cellular components. This program will dramatically extend the range of biomolecular systems that can be modelled with near atomistic precision. It will provide a better understanding of the structure and function of proteins involved in the regulation of membrane fusion and fission as well as shedding light on the assembly of large-scale protein-protein and protein-membrane complexes in general. The work will help place Australia at the forefront of developing simulation techniques in biomolecular systems, which are widely used within the chemical and pharmaceutical industries for modelling processes ranging from protein-drug interactions to the phase behaviour of lipids and surfactants. Read moreRead less
Learning to predict polymorphism through simulation of nucleation and nanoparticle evolution. Many substances are capable of exhibiting a myriad of different structures despite having the same composition. This behaviour can have a significant impact on the production of new pharmaceuticals, since the sudden appearance of a new form can lead to instant withdrawal of the drug. By understanding how different forms grow, rather than focusing on just the stability of the product, this research will ....Learning to predict polymorphism through simulation of nucleation and nanoparticle evolution. Many substances are capable of exhibiting a myriad of different structures despite having the same composition. This behaviour can have a significant impact on the production of new pharmaceuticals, since the sudden appearance of a new form can lead to instant withdrawal of the drug. By understanding how different forms grow, rather than focusing on just the stability of the product, this research will lead to more reliable prediction of how pharmaceutical molecules might assemble. The same technology will potentially have impacts in many areas of nanoscience through improvements in efficiency, including the production of minerals, desalination and undersea gas recovery.Read moreRead less
First Principles Design of Second-Generation Protein Stains. Proteomics is an emerging technology which has the potential to revolutionize modern biology and medicine. Extremely sensitive protein stains are a key proteomics technology, and in conjunction with gel electrophoresis, they facilitate the rapid and quantitative detection of all polypeptides in a cell. However, the tools of proteomics must rapidly advance (cheaper, greater sensitivity, more reliable, safer to handle) before the techn ....First Principles Design of Second-Generation Protein Stains. Proteomics is an emerging technology which has the potential to revolutionize modern biology and medicine. Extremely sensitive protein stains are a key proteomics technology, and in conjunction with gel electrophoresis, they facilitate the rapid and quantitative detection of all polypeptides in a cell. However, the tools of proteomics must rapidly advance (cheaper, greater sensitivity, more reliable, safer to handle) before the technology can mature to the stage where its full potential is realized. We will enable the evolution of proteomics by devising second generation fluorescent protein stains, using the environmentally-friendly natural product, epicocconone, as our design platform.Read moreRead less
Response of Proteins to External Non-Ionising Radiation: an Experimental and Computer Modelling Investigation. The expanding use of digital technologies such as mobile phones has led to major health concerns about the effects of non-ionising pulsed radiation exposure which has been shown to produce instantaneous temperature rises undetectable by normal thermometry. The health implications of exposure are not understandable without establishing molecular mechanisms by which pulsed microwaves can ....Response of Proteins to External Non-Ionising Radiation: an Experimental and Computer Modelling Investigation. The expanding use of digital technologies such as mobile phones has led to major health concerns about the effects of non-ionising pulsed radiation exposure which has been shown to produce instantaneous temperature rises undetectable by normal thermometry. The health implications of exposure are not understandable without establishing molecular mechanisms by which pulsed microwaves can cause biological effects. We aim to establish methods for studying the molecular mechanisms of protein structural and energetic changes occurring due to non-ionising radiation. The results will help our industry partner to design specific drugs as well as formulate a scientifically based standard for microwave utilisation.Read moreRead less
Self organization in (bio)molecular systems: Simulating the folding and aggregation of peptides, proteins and lipids. Molecular self-assembly is a basic property of living systems. Most proteins fold spontaneously and then further self-organize into functional complexes, effectively biological machines. Understanding how this occurs is a fundamental theoretical challenge with widespread application. Work will focus on developing methodology to simulate, computationally, the folding and aggrega ....Self organization in (bio)molecular systems: Simulating the folding and aggregation of peptides, proteins and lipids. Molecular self-assembly is a basic property of living systems. Most proteins fold spontaneously and then further self-organize into functional complexes, effectively biological machines. Understanding how this occurs is a fundamental theoretical challenge with widespread application. Work will focus on developing methodology to simulate, computationally, the folding and aggregation of peptides, proteins, and lipids. The aim is to accurately predict the structures of small peptides in solution and to refine crude models of larger molecules (complexes). This will facilitate the development of peptide based therapeutics and is essential in exploiting the growing volume of genetic information in biology and medicine.Read moreRead less
The First Chemically Accurate Tools in Theoretical Materials Research. Non-metallic materials are widely used in catalytic, separation and sensing applications. This project will create a new, accurate, general and systematic approach to the computational study of non-metallic materials and will provide an enormous step forward in our ability to design these materials for specific applications. With ever increasing demand, growing world population and shrinking natural resources, the benefits of ....The First Chemically Accurate Tools in Theoretical Materials Research. Non-metallic materials are widely used in catalytic, separation and sensing applications. This project will create a new, accurate, general and systematic approach to the computational study of non-metallic materials and will provide an enormous step forward in our ability to design these materials for specific applications. With ever increasing demand, growing world population and shrinking natural resources, the benefits of such rational materials design impact on the development of new, safer, more efficient, reusable materials in chemical, engineering, electronic and biological applications. Read moreRead less
TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protei ....TOWARDS A COMPLETE DESCRIPTION OF HOW ENZYMES WORK: development of simulation methods and protocols, blind test predictions, and experimental validation. Enzymes catalyze quite fantastic chemistry under mild physiological conditions. Many special chemical concepts (such as "transition-state stabilization" and "entropy-enthalpy compensation") proposed to explain these powers are unnecessary. Uniquely for a catalyst, these powers are integral to the structure, properties and dynamics of the protein, as constrained and selected by evolution. The question is how do they work? Answering this requires energetic and thermodynamic analysis beyond current experimental techniques, but accessible by computer simulation. We aim to develop a robust toolkit of simulation methods and protocols, blind test them by predicting the mechanism of a new enzyme, with followup experimental validation.
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Understanding dendrimer pharmaceuticals: The application of parallel computing to the investigation of dendrimer structure and activity. Dendrimers or starburst polymers are an important new class of synthetic material with physical and chemical properties that lie between those of small organic molecules and traditional linear polymers. One exciting area of application is the development of new dendrimer-based pharmaceuticals. This project aims to use computer-aided molecular modelling method ....Understanding dendrimer pharmaceuticals: The application of parallel computing to the investigation of dendrimer structure and activity. Dendrimers or starburst polymers are an important new class of synthetic material with physical and chemical properties that lie between those of small organic molecules and traditional linear polymers. One exciting area of application is the development of new dendrimer-based pharmaceuticals. This project aims to use computer-aided molecular modelling methods to investigate the three dimensional structure and dynamic behaviour of dendrimers. This will assist in the design of new compounds to target diseases such as secondary cancers, asthma and viral respiratory diseases.Read moreRead less