Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experim ....Dynamic Force Microscopy of small molecular assemblies. The possibility of manipulating a single molecule seems at first unreal, indeed 5 years ago it was pure science fiction. Through the gaining popularity of the Atomic Force Microscope (AFM) many perspectives about the molecular world are changing. Macroscopic effects such as adhesion and lubrication are now discussed in light of measurements made with this instrument. Newer work includes the observation of single protein unfolding experiments. The biophysics oriented project detailed in this application will extend the AFM: into multi-molecular systems formed by self-assembly, such as cell membranes; into polyelectrolyte-surface interactions; and, finally into the sequencing of DNA.Read moreRead less
Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production ....Disorder as a novel determinant of photosynthetic structure and function: an experimental study. Australia enjoys a world reputation in photosynthesis research, typified by hosting the 2001 International Photosynthesis Congress. It also has a claim to fame for theoretical work in non-equilibrium thermodynamics concerning production of disorder or entropy, yielding new insights into planetary climates. This experimental project investigates the novel relation between entropy/entropy production and the structure/function of the solar powerhouse of plants (chloroplasts), and addresses fundamental questions at the interface of biology and physics. The research explores chloroplasts as a manifestation of the all-pervading Second Law of Thermodynamics, advancing Australia's contribution to basic science and helping to train researchers.Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less
Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will c ....Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will construct a set of physical models of biological ion channels, which will correctly replicate experimental observations. Such a theory will link the structure and function of an ion channel through the fundamental principles of physics.Read moreRead less
New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less
New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-lig ....New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-ligand interactions at increased rates and enhanced accuracy. In addition, the three-dimensional structures of proteins and protein domains of biologically important functions and unknown fold will be determined by NMR. The project aims at techniques of direct impact in pharmaceutical industry.Read moreRead less
Comparative Biophysical Studies on Photosystem II of Higher Plants and Cyanobacteria. Photosystem II (PS-II) is one of two light trapping protein assemblies involved in the conversion of light into metabolic energy in all plants and algae. The manganese containing active site of PS-II is responsible for oxygen formation from water. The organisation and functioning of this centre and the detailed mechanism of photochemical energy conversion are not understood. This project will employ a combinati ....Comparative Biophysical Studies on Photosystem II of Higher Plants and Cyanobacteria. Photosystem II (PS-II) is one of two light trapping protein assemblies involved in the conversion of light into metabolic energy in all plants and algae. The manganese containing active site of PS-II is responsible for oxygen formation from water. The organisation and functioning of this centre and the detailed mechanism of photochemical energy conversion are not understood. This project will employ a combination of powerful biophysical techniques to probe the structure and mechanism of PS-II as a knowledge base for eventual genetic manipulation of plants and stategies for artificial photosynthesis.Read moreRead less
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
ARC Centre of Excellence - Coherent X-ray Science. The twenty first century is said to be the century of biology. And there is no doubt that the development of our understanding of biological system is continuing at a massive rate. However as our understanding deepens, we need to draw on the whole range of scientific disciplines to proceed. This Centre draws together a multidisciplinary team of world-leading scientists to address one the key questions in modern biology, the structure of a membra ....ARC Centre of Excellence - Coherent X-ray Science. The twenty first century is said to be the century of biology. And there is no doubt that the development of our understanding of biological system is continuing at a massive rate. However as our understanding deepens, we need to draw on the whole range of scientific disciplines to proceed. This Centre draws together a multidisciplinary team of world-leading scientists to address one the key questions in modern biology, the structure of a membrane protein. We will develop techniques based on the latest developments in theoretical physics & chemistry, imaging, biology and technology - including the new Australian Synchrotron - to create new approaches to structural biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346876
Funder
Australian Research Council
Funding Amount
$1,584,000.00
Summary
800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resol ....800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resolution problems will become tractable. The increased turn-around times afforded by the high sensitivity of the cryo-enabled spectrometer make it possible to provide access for Australian institutions that would not otherwise have access to comparable equipment.Read moreRead less