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
Persistent Triplet Carbenes. Viable or Not? Triplet carbenes have significant potential real world applications, such as in modern electronics. However, they are highly reactive (lifetimes typically < 1 day), and this has stymied their development. Can I design so called persistent triplet-carbenes, which have significant lifetimes? I will try to using computer chemistry. In doing so, I will provide synthetic chemists with 'high-value' targets for preparation, hence saving tax dollars and minimi ....Persistent Triplet Carbenes. Viable or Not? Triplet carbenes have significant potential real world applications, such as in modern electronics. However, they are highly reactive (lifetimes typically < 1 day), and this has stymied their development. Can I design so called persistent triplet-carbenes, which have significant lifetimes? I will try to using computer chemistry. In doing so, I will provide synthetic chemists with 'high-value' targets for preparation, hence saving tax dollars and minimizing creation of environmentally damaging waste. Read moreRead less
The elusive upper bound of heat transfer in horizontal convection. The question as to whether lateral variation in global ocean buoyancy resulting from low solar radiation near the poles and higher temperatures in the tropical regions (known as horizontal convection) is a driver for global ocean currents is critical to our understanding of this complex and delicate system that maintains Earth's temperate climate. This question hinges on the relationship between heat transport and strength of buo ....The elusive upper bound of heat transfer in horizontal convection. The question as to whether lateral variation in global ocean buoyancy resulting from low solar radiation near the poles and higher temperatures in the tropical regions (known as horizontal convection) is a driver for global ocean currents is critical to our understanding of this complex and delicate system that maintains Earth's temperate climate. This question hinges on the relationship between heat transport and strength of buoyancy forcing towards global scales; this project proposes a landmark experimental effort supported by detailed simulations to probe the ultimate regime of heat transport in horizontal convection. The project is expected to inform the direction of future ocean and climate modelling efforts to the benefit of humanity.Read moreRead less
Voids in molecular crystals: Novel computational approaches to their characterization, physicochemical nature, and influence on bulk properties. Key to the research objectives is further development of our own innovative software and techniques, now used by hundreds of researchers worldwide for the visualization and exploration of the structure and properties of molecular crystals. Through involvement of postdoctoral fellows and PhD students in an international collaborative research program inv ....Voids in molecular crystals: Novel computational approaches to their characterization, physicochemical nature, and influence on bulk properties. Key to the research objectives is further development of our own innovative software and techniques, now used by hundreds of researchers worldwide for the visualization and exploration of the structure and properties of molecular crystals. Through involvement of postdoctoral fellows and PhD students in an international collaborative research program involving a synergy between software development and visualization, and sophisticated modelling of the detailed nature of molecular crystals, the project contributes directly to producing researchers familiar with state-of-the-art theoretical and computational techniques, and well equipped to match the needs of one of the nation's articulated research priorities.Read moreRead less
Computational Nanofluidics. This project will generate an increased level of skill and expertise in Australia in the emerging science of nanotechnology. To realise the promise of nanotechnology, a means of controlled propulsion on the nano scale is vital. A deeper understanding of nanofluidics that allows greater predictive capacities can greatly aid this realisation. It is highly likely that computational nanofluidics will play as important a role in nanotechnology based industries as computat ....Computational Nanofluidics. This project will generate an increased level of skill and expertise in Australia in the emerging science of nanotechnology. To realise the promise of nanotechnology, a means of controlled propulsion on the nano scale is vital. A deeper understanding of nanofluidics that allows greater predictive capacities can greatly aid this realisation. It is highly likely that computational nanofluidics will play as important a role in nanotechnology based industries as computational fluid dynamics (CFD) currently plays in today's manufacturing, automotive and aerospace industries. The skills and knowledge gained from this project will enhance our international competitiveness in this area. Read moreRead less
On the mechanism of boiling instability in microchannels. This project will enable designers to create highly efficient miniaturised devices based on the boiling of fluids such as water or organics. These devices include micro-power generation systems, coolers for computer chips and solar collectors, and micro-chemical process systems. Such devices provide environmental, safety and economic benefits.
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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Importance of conformational and electrostatic contributions in simulations of enzyme reaction mechanisms. The research will contribute to the development of biomolecular simulation in Australia by demonstrating its potential to complement experiment, and also promote the effective use of APAC (Australian national supercomputer facilities) resources by providing advanced programs and computational protocols for other researchers. It will assist the diffusion of computational biology technology i ....Importance of conformational and electrostatic contributions in simulations of enzyme reaction mechanisms. The research will contribute to the development of biomolecular simulation in Australia by demonstrating its potential to complement experiment, and also promote the effective use of APAC (Australian national supercomputer facilities) resources by providing advanced programs and computational protocols for other researchers. It will assist the diffusion of computational biology technology into industrial applications such as rational drug design and protein engineering, as, for example, in our associated Linkage project grant, and provide novel insights into protein engineering and other sorts of design, which transcend concepts currently used in biomimetic chemistry.Read moreRead less
Robust Reformulation Methods. Many decision problems in engineering, business and economics are modeled as nonlinear continuous optimization problems. Often these are made difficult by the existence of constraints. In this project, we reformulate such problems as constrained nonsmooth equations, rather than optimization problems, and develop generalized Newton and quasi-Newton methods for solving them. The expected outcomes of this project include a systematic theory of reformulation methods, ....Robust Reformulation Methods. Many decision problems in engineering, business and economics are modeled as nonlinear continuous optimization problems. Often these are made difficult by the existence of constraints. In this project, we reformulate such problems as constrained nonsmooth equations, rather than optimization problems, and develop generalized Newton and quasi-Newton methods for solving them. The expected outcomes of this project include a systematic theory of reformulation methods, and robust and efficient algorithms for solving some important nonlinear continuous optimization problems. There is high potential for applications in engineering, business and finance.Read moreRead less