A5034865500- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Supramolecular Self-Assembly in Materials
- Biochemical and Molecular Research
- Antimicrobial Peptides and Activities
- RNA and protein synthesis mechanisms
- Receptor Mechanisms and Signaling
- Polydiacetylene-based materials and applications
- Influenza Virus Research Studies
- Analytical Chemistry and Chromatography
- Ion channel regulation and function
- Graphene and Nanomaterials Applications
- Cardiac electrophysiology and arrhythmias
- Glycosylation and Glycoproteins Research
- HIV/AIDS drug development and treatment
- Alzheimer's disease research and treatments
- Marine Invertebrate Physiology and Ecology
- Estrogen and related hormone effects
- Click Chemistry and Applications
- Enzyme Structure and Function
- Diatoms and Algae Research
- Electrochemical Analysis and Applications
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
RMIT University
2021-2024
MIT University
2021-2023
Monash University
2017-2022
Griffith University
2018
Bond University
2017
Underpinning all drug discovery projects is the interaction between a and its target, usually protein. Thus, improved methods for predicting magnitude of protein–ligand interactions have potential to improve efficiency development. In this review, we describe principles free energy used calculation binding energies, challenges associated with these methods, recent advances developed address difficulties. We then present case studies from 2005 2017, each demonstrating that alchemical can...
Peptide self-assembly is the process by which peptide molecules aggregate into low dimensional (1D, 2D) or 3D ordered materials with potential applications ranging from drug delivery to electronics. Short peptides are particularly good candidates for forming supramolecular assemblies due relatively simple structure and ease of modulating their achieve required material properties. The experimental resolution fibrous peptide-based nanomaterials as atomic coordinates remains challenging. For...
The fine tuning of biological electrical signaling is mediated by variations in the rates opening and closing gates that control ion flux through different channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to role they play regulating cardiac activity. Here, we exploit K
Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas largely unexplored chemical space. To shape our understanding the interaction between natural protein targets in postgenomic era, we have used native mass spectrometry investigate 62 potential malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight identified as binding partners 32 putative malarial targets. Seventy-nine (79)...
A wide range of drug targets can be effectively modulated by peptides and macrocycles. Unfortunately, the size polarity these compounds prevents them from crossing cell membrane to reach target sites in cytosol. As such, do not conform standard measures drug-likeness exist beyond rule-of-five space. In this work, we investigate whether prodrug moieties that mask hydrogen bond donors applied domain improve permeation macrocyclic compounds. Using a cyclic peptide model, show masking natural...
The novel RNA virus, severe acute respiratory syndrome coronavirus II (SARS-CoV-2), is currently the leading cause of mortality in 2020, having led to over 1.6 million deaths and infecting 75 people worldwide by December 2020. While vaccination has started several clinical trials for a number vaccines are underway, there pressing need cure those already infected with virus. Of particular interest design anti-SARS-CoV-2 therapeutics human protein angiotensin converting enzyme (ACE2) which...
The ability to predict cell-permeable candidate molecules has great potential assist drug discovery projects. Large that lie beyond the Rule of Five (bRo5) are increasingly important as candidates and tool for chemical biology. However, such large usually do not cross cell membranes cannot access intracellular targets or be developed orally bioavailable drugs. Here, we describe a random forest (RF) machine learning model prediction passive membrane permeation rates using set over 1000 bRo5...
Cell–cell communication via endogenous peptides and their receptors is vital for controlling all aspects of human physiology most signal through G protein-coupled (GPCRs). Disordered bind GPCRs complex modes which there are few representative crystal structures. The disordered peptide neurotensin (NT) a neuromodulator classical neurotransmitters such as dopamine glutamate, activation receptor 1 (NTS1). While several experimental structures show how NT binds NTS1, details about the structural...
SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated targeted for degradation. Inhibition of this interaction increases levels, consequently cellular (NO) concentrations, has been proposed as a potential strategy killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 CP2) potent inhibitors murine SPSB–iNOS interaction. In study, we report...
β-Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability self-assemble into low dimensional nanostructures, resistance enzymatic degradation in vivo. However, the self-assembly mechanisms of β-peptides, which possess increased flexibility extra backbone methylene groups present within constituent β-amino acids, are not well understood inherent difficulties observing bottom-up growth pathway experimentally. A computational approach is presented...
Human amylin is an inherently disordered protein whose ability to form amyloid fibrils linked the onset of type II diabetes. Graphitic nanomaterials have potential in managing diseases as they can disrupt aggregation processes biological settings, but optimising these materials prevent fibrillation challenging. Here, we employ bias-exchange molecular dynamics simulations systematically study structure and adsorption preferences on graphitic nanoflakes that vary their physical dimensions...
The p75 splice variant of lens epithelium-derived growth factor (LEDGF) is a 75 kDa protein, which recruited by the human immunodeficiency virus (HIV) to tether pre-integration complex host chromatin and promote integration proviral DNA into genome. We designed series small cyclic peptides that are structural mimics LEDGF binding domain, interact with integrase as potential inhibitors. Herein we present X-ray crystal structures, NMR studies, SPR analysis, conformational studies four bound...
Abstract The fine tuning of biological electrical signaling is mediated by variations in the rates opening and closing gates that control ion flux through different channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to role they play regulating cardiac activity. Here, we exploited K + sensitivity HERG determine structures both a conductive non-conductive selectivity filter structure HERG. We propose result high...
Accurate methods to predict the free energies of protein-ligand interactions have great potential assist rational drug design. In this work, we used molecular dynamics simulations with alchemical perturbation binding carbohydrate-based ligands influenza virus neuraminidase (N2). This specific target is a challenging test system for energy because it has flexible site motifs. We use protocol that works longer time scales than are often reported in previous studies N2. demonstrated N2-ligand...
Accurate methods to predict the free energies of protein-ligand interactions have great potential assist rational drug design. In this work, we used molecular dynamics simulations with alchemical perturbation binding carbohydrate-based ligands influenza virus neuraminidase (N2). This specific target is a challenging test system for energy because it has flexible site motifs. We use protocol that works longer time scales than are often reported in previous studies N2. demonstrated N2-ligand...