A5032082476- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- Spectroscopy and Quantum Chemical Studies
- Genomics and Phylogenetic Studies
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
- Proteins in Food Systems
- Antimicrobial Peptides and Activities
- Science Education and Pedagogy
- Advanced NMR Techniques and Applications
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Mass Spectrometry Techniques and Applications
- Teaching and Learning Programming
- Educational Games and Gamification
- Machine Learning in Bioinformatics
- PI3K/AKT/mTOR signaling in cancer
- Pickering emulsions and particle stabilization
- NMR spectroscopy and applications
- Biochemical and Structural Characterization
Maurice Wilkins Centre
2015-2024
University of Auckland
2015-2024
University of Canterbury
2015-2023
Massey University
2012-2020
University of Cambridge
2009-2014
ETH Zurich
2011-2013
École Polytechnique Fédérale de Lausanne
2009-2012
Novartis (Switzerland)
1979
GROMOS++ is a set of C++ programs for pre- and postprocessing molecular dynamics simulation trajectories as such part the GROningen MOlecular Simulation software (bio)molecular simulation. It contains more than 70 that can be used to prepare data production analyze these. These are reviewed various structural, dynamic, thermodynamic quantities analyzed using time series, correlation functions, distributions described together with technical aspects their implementation in GROMOS. A few...
Natively unfolded proteins present a challenge for structure determination because they populate highly heterogeneous ensembles of conformations. A useful source structural information about these states is provided by paramagnetic relaxation enhancement measurements nuclear magnetic resonance spectroscopy, from which long-range interatomic distances can be estimated. Here we describe method using such as restraints in molecular dynamics simulations to obtain mapping the free energy...
For molecular dynamics simulations of biological membrane systems to live up the potential providing accurate atomic level detail into properties and functions, it is essential that force fields used model such are as possible. One property often assess field accuracy carbon-hydrogen (or carbon-deuterium) order parameters lipid tails, which can be accurately measured using experimental NMR techniques. There a variety analysis tools available calculate these from computational work correctly...
Abstract In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential nutrients. TRAP receive their substrates via a secreted soluble substrate-binding protein. How sodium ion-driven secondary active transporter is strictly coupled to protein poorly understood. Here we report the cryo-EM structure of sialic acid SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM comprises “transport” domain “scaffold” domain, with transport consisting...
Abstract Since the most recent description of functionalities GROMOS software for biomolecular simulation in 2005 many new functions have been implemented. In this article, that involve modified forces a molecular dynamics (MD) are described: treatment electronic polarizability, an implicit surface area and internal volume solvation term to calculate interatomic forces, coarse‐grained supramolecular force field, multiplicative switching function nonbonded interactions, adiabatic decoupling...
α-Synuclein is an intrinsically disordered protein whose aggregation implicated in Parkinson's disease. A second member of the synuclein family, β-synuclein, shares significant sequence similarity with α-synuclein but much more resistant to aggregation. β-Synuclein missing 11-residue stretch central non-β-amyloid component region that forms core amyloid fibrils, yet insertion these residues into β-synuclein produce βSHC construct does not markedly increase propensity. To investigate...
Controlling and manipulating protein behavior at an interface is of immense relevance to a broad range physicochemical biological phenomena technological processes. Although many experimental studies have contributed rapid progress in the fundamental knowledge interfaces, detailed molecular-level understanding mechanism adsorption still remarkably lacking. In this study, atomistic molecular dynamics simulations were used characterize β-lactoglobulin two different oil/water (O/W) where oil...
Abstract Protein structure is more conserved than protein sequence, and therefore may be useful for phylogenetic inference beyond the “twilight zone” where sequence similarity highly decayed. Until recently, structural phylogenetics was constrained by lack of solved structures most proteins, reliance on distance methods which made it difficult to treat uncertainty statistically. AlphaFold has mostly overcome first problem making predictions readily available. We address second redeploying a...
Mammalian cell surfaces are decorated with complex glycoconjugates that terminate negatively charged sialic acids. Commensal and pathogenic bacteria can use host-derived acids for a competitive advantage, but require functional acid transporter to import the sugar into cell. This work investigates sodium symporter (SiaT) from Staphylococcus aureus (SaSiaT). We demonstrate SaSiaT rescues an Escherichia coli strain lacking its endogenous when grown on N-acetylneuraminic (Neu5Ac) or...
ABSTRACT A key learning outcome for undergraduate biochemistry classes is a thorough understanding of the principles protein structure. Traditional approaches to teaching this material, which include two‐dimensional (2D) images on paper, physical molecular modeling kits, and projections 3D structures into 2D, are unable fully capture dynamic nature proteins. We have built virtual reality application, Peppy, aimed at facilitating secondary Rather than attempt model molecules with same...
Antimicrobial peptides (AMPs) are a potential solution to the increasing threat of antibiotic resistance, but successful design active nontoxic AMPs requires understanding their mechanism action. Molecular dynamics (MD) simulations can provide atomic-level information regarding how interact with cell membrane. Here, we have used MD study two linear analogs battacin, naturally occurring cyclic, lipidated, nonribosomal AMP. Like these against Gram-negative multidrug resistant and Gram-positive...
Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP provide broad framework understand how they work, but the mechanistic details transport not yet defined. Here we report cryo-EM structure Haemophilus influenzae N -acetylneuraminate transporter ( Hi SiaQM) at 2.99 Å...
Abstract Enzymes are nature's catalysts, mediating chemical processes in living systems. The study of enzyme function and mechanism includes defining the maximum catalytic rate affinity for substrate/s (among other factors), referred to as kinetics. Enzyme kinetics is a staple biochemistry curricula disciplines, from molecular cellular biology pharmacology. However, because involves concepts rarely employed areas biology, it can be challenging students researchers. Traditional graphical...
The remarkable recent creation of two proteins that fold into completely different and stable structures, exhibit functions, yet differ by only a few amino acids poses conundrum to those hoping understand how sequence encodes structure. Here, computer modeling uniquely allows the characterization not native structure each minimally but also systems in which was modeled onto alternate sequence. reasons for structural preferences pairs highly similar sequences are explored combination...
Abstract Successful progression through the cell cycle requires spatial and temporal regulation of gene transcript levels number, positions condensation chromosomes. Here we present a high resolution survey genome interactions in Schizosaccharomyces pombe using synchronized cells to investigate dependent changes organization transcription. Cell were captured between within S. Known features (e.g. clustering telomeres retrotransposon long terminal repeats (LTRs)) observed throughout cycle....
Abstract For evaluating the deepest evolutionary relationships among proteins, sequence similarity is too low for application of sequence-based homology search or phylogenetic methods. In such cases, comparison protein structures, which are often better conserved than sequences, may provide an alternative means uncovering deep signal. Although major structure databases as SCOP and CATH hierarchically group they do not describe specific within a hierarchical level. Structural phylogenies have...
Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP provide broad framework understand how they work, but the mechanistic details transport not yet defined. Here we report cryo-EM structure Haemophilus influenzae N-acetylneuraminate transporter (HiSiaQM) at 2.99 Å resolution...
The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion the alphabet would have enhanced their capabilities, fostering metabolic prowess organismal fitness early living systems. While addition bearing innovative directly enhances chemical proteomes, inclusion chemically redundant monomers is difficult to...