ORCID Profile
0000-0002-5699-1726
Current Organisation
The University of Auckland
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Publisher: American Chemical Society (ACS)
Date: 25-04-2016
DOI: 10.1021/ACS.BIOMAC.5B01709
Abstract: Controlling and manipulating protein behavior at an interface is of immense relevance to a broad range of physicochemical and biological phenomena and technological processes. Although many experimental studies have contributed to rapid progress in the fundamental knowledge of protein behavior at interfaces, detailed molecular-level understanding of the mechanism of protein adsorption at an interface is still remarkably lacking. In this study, atomistic molecular dynamics simulations were used to characterize the adsorption of β-lactoglobulin at two different oil/water (O/W) interfaces, where the oil was either the marginally hydrophilic octanol or the more hydrophilic triolein, and the results were compared to those of a previous study utilizing the hydrophobic oil decane. Both the approach to the surface and the mechanism of adsorption depend upon the hydrophilicity of the oil and the interfacial tension of the O/W interface, with the nature of the adsorption, the accompanying structural changes, and the energetic driving force differing markedly between the different oils. Intriguingly, the behavior of the protein resembles that predicted for a soft spherical particle at an O/W interface. The results are also in agreement with key experimental findings, particularly the observation that proteins undergo more conformational change upon adsorption to hydrophobic surfaces, flattening out to expose hydrophobic interior residues to the surface, and that a thicker layer of native-like adsorbed protein forms at hydrophilic surfaces, and reveal structural and mechanistic detail behind each mechanism of adsorption.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SC01814G
Abstract: We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology.
Publisher: Wiley
Date: 08-11-2016
Abstract: During the past half century, the number and accuracy of experimental techniques that can deliver values of observables for biomolecular systems have been steadily increasing. The conversion of a measured value Q
Publisher: Wiley
Date: 11-11-2019
DOI: 10.1002/PRO.3752
Abstract: A key learning outcome for undergraduate biochemistry classes is a thorough understanding of the principles of protein structure. Traditional approaches to teaching this material, which include two‐dimensional (2D) images on paper, physical molecular modeling kits, and projections of 3D structures into 2D, are unable to fully capture the dynamic 3D nature of proteins. We have built a virtual reality application, Peppy, aimed at facilitating teaching of the principles of protein secondary structure. Rather than attempt to model molecules with the same fidelity to the underlying physical chemistry as existing, research‐oriented molecular modelling approaches, we took the more straightforward approach of harnessing the Unity video game physics engine. Indeed, the simplicity and limitations of our model are strengths in a teaching context, provoking questions and thus deeper understanding. Peppy allows exploration of the relative effects of hydrogen bonding (and electrostatic interactions more generally), backbone φ/ψ angles, basic chemical structure, and steric effects on a polypeptide structure in an accessible format that is novel, dynamic, and fun to use. Apart from describing the implementation and use of Peppy, we discuss the outcomes of deploying Peppy in undergraduate biochemistry courses.
Publisher: Wiley
Date: 08-11-2016
Publisher: ACM
Date: 09-10-2023
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/JEB.228239
Abstract: In honeybees there are three alleles of cytosolic malate dehydrogenase: F, M and S. Allele frequencies are correlated with environmental temperature, suggesting that the alleles have temperature-dependent fitness benefits. We determined the enzymic activity of each allele across a range of temperatures in vitro. The F and S alleles have higher activity and are less sensitive to high temperatures than the M allele, which loses activity after incubation at temperatures found in the thorax of foraging bees in hot climates. Next, we predicted the protein structure of each allele and used molecular dynamics simulations to investigate their molecular flexibility. The M allele is more flexible than the S and F alleles at 50°C, suggesting a plausible explanation for M's loss of activity at high temperatures, and has the greatest structural flexibility at 15°C, suggesting that it can retain some enzyme activity at cooler temperatures. MM bees recovered from two hours of cold narcosis significantly better than all other genotypes. Combined, these results explain clinal variation in MDH allele frequencies in the honeybee at the molecular level.
Publisher: American Chemical Society (ACS)
Date: 26-05-2015
DOI: 10.1021/ACS.BIOMAC.5B00467
Abstract: Protein adsorption at liquid-liquid interfaces is of immense relevance to many biological processes and dairy-based functional foods. Due to experimental limitations, however, there is still a remarkable lack of understanding of the adsorption mechanism, particularly at a molecular level. In this study, atomistic molecular dynamics simulations were used to elucidate the approach and adsorption mechanism of β-lactoglobulin (β-LG) at a decane-water interface. Through multiple independent simulations starting from three representative initial orientations of β-LG relative to the decane surface the rate at which β-LG approaches the oil/water interface is found to be independent of its initial orientation, and largely stochastic in nature. While the residues that first make contact with the decane and the final orientation of β-LG upon adsorption are similar in all cases, the adsorption process is driven predominantly by structural rearrangements that preserve the secondary structure but expose hydrophobic residues to the decane surface. This detailed characterization of the adsorption of β-LG at an oil/water interface should inform the design and development of novel encapsulation and delivery systems in the food and pharmaceutical sciences.
Publisher: Elsevier BV
Date: 03-2020
Publisher: AIP Publishing
Date: 19-04-2021
DOI: 10.1063/5.0045115
Abstract: Cyclodextrins have a erse range of applications, including as supramolecular hosts, as enzyme active-site analogs, in improving drug solubility and delivery, and in molecular selection. We have investigated their ability to form stable complexes with bullvalenes, unusual organic cage molecules that spontaneously interconvert between numerous degenerate isomers. The shape-shifting nature of substituted bullvalenes raises the potential for dynamic adaptive binding to biological targets. We tested whether β- and γ-cyclodextrins can capture particular bullvalene isomers and whether the preferred binding mode(s) differ between isomers. We first applied our computational host–guest interaction potential energy profiling to determine the best binding mode(s) of unsubstituted bullvalene and each isomer of methylenehydroxybullvalene to β- and γ-cyclodextrin. Subsequent molecular dynamics simulations of the predicted host–guest complexes showed that while unsubstituted bullvalene has a single, albeit ill-defined, binding mode with either cyclodextrin, each isomer of methylenehydroxybullvalene has two possible modes of binding to β-cyclodextrin but only a single, nebulous mode of binding to γ-cyclodextrin. Experimental determination of the binding free energy of each methylenehydroxybullvalene–cyclodextrin complex showed that methylenehydroxybullvalene is more likely to bind to β-cyclodextrin than to γ-cyclodextrin, despite its smaller cavity. Together, our results suggest that β-cyclodextrin, but not γ-cyclodextrin, shows promise for conformational capture of mono-substituted bullvalenes. More broadly, our computational pipeline should prove useful for rapid characterization of cyclodextrin host–guest complexes, avoiding the need for costly synthesis of guest molecules that are unlikely to bind stably, as well as providing detailed atomic-level insight into the nature of complexation.
Publisher: American Chemical Society (ACS)
Date: 22-11-2022
DOI: 10.1021/ACSINFECDIS.1C00347
Abstract: With the post-antibiotic era rapidly approaching, many have turned their attention to developing new treatments, often by structural modification of existing antibiotics. Polymyxins, a family of lipopeptide antibiotics that are used as a last line of defense in the clinic, have recently developed resistance and exhibit significant nephrotoxicity issues. Using thiol-ene chemistry, the facile preparation of six unique S-lipidated building blocks was demonstrated and used to generate lipopeptide mimetics upon incorporation into solid-phase peptide synthesis (SPPS). We then designed and synthesized 38 polymyxin analogues, incorporating these unique building blocks at the N-terminus, or to replace hydrophobic residues at positions 6 and 7 of the native lipopeptides. Several polymyxin analogues bearing one or more S
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2019
End Date: 2022
Funder: Human Frontier Science Program
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