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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
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
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
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