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
Characterising and exploiting hydrogen tunnelling in environmentally and medically important enzymes. Theory and experiment will be used to study environmentally and medically important enzymes, and quantify the role that hydrogen tunnelling plays in their activity. The project will determine the basis of their remarkable ability to catalyse chemical reactions, and to engineer and design more efficient proteins and pharmaceuticals.
Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum- ....Why is the photosynthetic CO2-fixing enzyme, Rubisco, so inefficient? Dissection of the catalytic chemistry by computational simulation and experimental testing. Fixation of CO2 by the enzyme Rubisco during photosynthesis produces organic compounds which feed all life. Despite this critical role, Rubisco catalyses its reaction sluggishly and, worse, discriminates poorly between CO2 and O2, leading to useless products. Our combined expertise equips us to analyse Rubisco's mechanism using quantum-chemical methods and then test predictions experimentally. We will capitalise on our previous successful studies of Rubisco by addressing emergent issues which are the keys to understanding catalytic efficiency and CO2/O2 selectivity: the roles of a carbamylated lysine; the way CO2 addition is rendered irreversible; and the spin inversion inherent in O2 addition.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0344441
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain ....New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain internationally competitive through the application of modern MCD spectroscopic techniques to the study of metal-centred biomolecules. These facilities will drive a number of programs in the area of metalloenzyme and photosystem II research.Read moreRead less
Structural and Mechanistic Studies of the Oxygen Evolving Centre in Photosystem II. Hydrogen fuel production from electricity and water sources, such as sea water, represents the ultimate goal for the research described here. This is part of an overall scheme, called "Artificial Photosynthesis", to generate clean renewable energy. The present project is an important step in this ambitious program and directly addresses a key hurdle which must be overcome to make artificial photosynthesis feasibl ....Structural and Mechanistic Studies of the Oxygen Evolving Centre in Photosystem II. Hydrogen fuel production from electricity and water sources, such as sea water, represents the ultimate goal for the research described here. This is part of an overall scheme, called "Artificial Photosynthesis", to generate clean renewable energy. The present project is an important step in this ambitious program and directly addresses a key hurdle which must be overcome to make artificial photosynthesis feasible. This hurdle is the efficient electrical conversion of water into hydrogen and oxygen, a two part process of which the latter is the most chemically difficult. The project aims to 'steal nature's secrets', by deciphering and then technologically mimicking the highly efficient means by which plants carry out these processes.Read moreRead less
Bio-Physical Studies of the Oxygen Evolving Complex in Photosystem II. Hydrogen fuel production from electricity and water sources, such as sea water, represents the ultimate goal for the research described here. This is part of an overall scheme, called "Artificial Photosynthesis", to generate clean renewable energy. The present project is an important step in this ambitious program and directly addresses a key hurdle which must be overcome to make artificial photosynthesis feasible. This hurdl ....Bio-Physical Studies of the Oxygen Evolving Complex in Photosystem II. Hydrogen fuel production from electricity and water sources, such as sea water, represents the ultimate goal for the research described here. This is part of an overall scheme, called "Artificial Photosynthesis", to generate clean renewable energy. The present project is an important step in this ambitious program and directly addresses a key hurdle which must be overcome to make artificial photosynthesis feasible. This hurdle is the efficient electrical conversion of water into hydrogen and oxygen, a two part process of which the latter is the most chemically difficult. The project aims to 'steal nature's secrets', by deciphering and then technologically mimicking the highly efficient means by which plants carry out these processes.Read moreRead less
Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poison ....Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poisoning. However, OP degrading enzymes could be improved in many ways - we will evolve these enzymes to enhance their catalytic properties - to enable them to act more efficiently on an increased number of OPs. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100181
Funder
Australian Research Council
Funding Amount
$650,000.00
Summary
Strengthening merit-based access and support at the new National Computing Infrastructure petascale supercomputing facility. World-leading high-performance computing is fundamental to Australia's international research success. This facility will provide access to the new National Computational Infrastructure facility by world-leading researchers from six research universities, and sustain ground-breaking work in an increasingly competitive environment.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100177
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ....Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ACT region devoted to the broad range of activities summarised above. A particular focus involves novel, biologically inspired energy systems and high efficiency solar cell technology.Read moreRead less