Surface ligation of nanomaterials for biomedical applications . The project aims to explore the synergistic effects co-ligands for target recognition and biofouling protection in nanoparticle surface patterns to enable practical atomic scale precision engineering of efficient and biofouling resistant nanosensors. The project will fundamentally characterise interfacial interactions and dynamics of ligated nano-surfaces and biomolecules via advanced computer modelling. Outcomes should include pra ....Surface ligation of nanomaterials for biomedical applications . The project aims to explore the synergistic effects co-ligands for target recognition and biofouling protection in nanoparticle surface patterns to enable practical atomic scale precision engineering of efficient and biofouling resistant nanosensors. The project will fundamentally characterise interfacial interactions and dynamics of ligated nano-surfaces and biomolecules via advanced computer modelling. Outcomes should include practical molecular design guidelines for functional ligands and predicted optimal patterns for combining functional and antifouling ligands on gold nanomaterials for biosensing technologies. The advanced predictive modelling capabilities will facilitate future practical engineering of efficient biomedical devices.Read moreRead less
Enhanced force fields for computational drug design and materials research. This project aims to improve the atomic interaction functions used to calculate the structural, dynamic and thermodynamic properties of molecules that alter net charge or structure in different environments. Predicting the stability of alternative protonation and tautomeric states for molecules bound to therapeutic targets is a major challenge in computational drug design. It is key to identifying the therapeutically act ....Enhanced force fields for computational drug design and materials research. This project aims to improve the atomic interaction functions used to calculate the structural, dynamic and thermodynamic properties of molecules that alter net charge or structure in different environments. Predicting the stability of alternative protonation and tautomeric states for molecules bound to therapeutic targets is a major challenge in computational drug design. It is key to identifying the therapeutically active chemical species as well as understanding drug transport and off-target effects. The work will expand the utility of modelling software used by over 13,000 researchers worldwide. In addition, the improved interaction functions will also help in the understanding of a wide range of other materials at an atomic level.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.Read moreRead less
Pushing The Boundaries Of Flow Chemistry – Towards New Anti-Viral Agents. Synthetic chemistry approaches to new drugs rely on access to robust reliable reactions. Traditionally these approaches are highly wasteful with the pharmaceutical industries producing five to a hundred kilograms of waste per kilogram of product. Total flow chemistry approaches will significantly reduce waste, allow rapid reaction sequence optimisation, and seamless scale up. In a collaborative effort spanning Australia, G ....Pushing The Boundaries Of Flow Chemistry – Towards New Anti-Viral Agents. Synthetic chemistry approaches to new drugs rely on access to robust reliable reactions. Traditionally these approaches are highly wasteful with the pharmaceutical industries producing five to a hundred kilograms of waste per kilogram of product. Total flow chemistry approaches will significantly reduce waste, allow rapid reaction sequence optimisation, and seamless scale up. In a collaborative effort spanning Australia, Germany and the USA, in an exemplar of a real world application, this project will produce benefits not only in enhanced and greener synthetic approaches, but also in the development of strategies for the identification of small molecules, the precursors to a new mode of action class of anti-viral drugs.Read moreRead less
Exploring the novel structural features of influenza virus sialidase. The outcomes of this project will provide a deeper mechanistic understanding of influenza virus sialidase and the importance of the enzyme's flexible loops in carbohydrate recognition. Specifically, this project will improve our understanding of fundamental aspects of inhibitor binding by influenza virus sialidases.
Ultrasound-assisted fabrication of biofunctional materials. The project aims to develop a fundamental understanding of the mechanism involved in the synthetic process in order to control the physical and functional properties of core-shell biomaterials. Biofunctional core-shell materials are of scientific interest due to their potential use in a variety of applications including food manufacturing. Among existing methodologies for the synthesis of core-shell biomaterials, ultrasonic technology o ....Ultrasound-assisted fabrication of biofunctional materials. The project aims to develop a fundamental understanding of the mechanism involved in the synthetic process in order to control the physical and functional properties of core-shell biomaterials. Biofunctional core-shell materials are of scientific interest due to their potential use in a variety of applications including food manufacturing. Among existing methodologies for the synthesis of core-shell biomaterials, ultrasonic technology offers versatility and a wider choice of core and shell materials possessing specific biofunctionality. The outcomes of this project may include the establishment of a versatile technology for the fabrication of tailor-made biofunctional materials suitable for specific applications.Read moreRead less
Natural product scaffolds: an approach to privileged structures. Based on the fact that nature has provided approximately 50 per cent of current drugs, the purpose of this project is to identify scaffolds that are critical for the biological interactions. The expected outcome is to build libraries based on the scaffolds and identify new privileged structures for application in drug discovery.
Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or ot ....Force Fields for Structure Refinement and Computational Drug Design. The ability to model molecular systems at an atomic level, as used in protein structure refinement or computational drug design, is critically dependent on the accuracy with which inter-atomic interactions are represented. Highly optimised and well-validated interaction parameters are available for common biomolecules, such as amino acids, sugars and lipids, but not for co-factors, substrates and potential drug molecules, or other molecules of interest such as polymers and dendrimers. The aim of this project is to develop and validate geometric and interaction parameters (force fields) for complex organic molecules and use these to facilitate bio-molecular structure refinement and computational drug design.Read moreRead less
Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both con ....Improving empirical force fields: a big-data approach. This project aims to improve the ability to represent the thermodynamic properties of molecules of biological, pharmaceutical or materials interest by developing force fields capable of describing a diverse range of molecules both consistently and with high fidelity. The project aims to exploit a rapidly expanding, in-house database of parameterized molecular structures to develop highly optimised, well-validated parameters that are both consistent and transferable, enabling molecules of any size or complexity to be parameterised with a fidelity currently only possible for simple organics. This will provide significant benefits, such as helping to improve the accuracy and reliability of ligand: protein complexes determined experimentally, a limiting factor in computational drug design.Read moreRead less
Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expecte ....Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expected outcomes include new tools which quickly inform medicinal chemists how drugs interact with their targets and how they can be improved. The developed tools should provide significant benefit to many researchers by accelerating the early stage of drug discovery, and support Australia’s fast growing biotechnology sector.Read moreRead less