Daniel A. Holdbrook

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Bacterial membranes are complex organelles composed of a variety of lipid types. The differences in their composition are a key factor in determining their relative permeabilities. The success of antibacterial agents depends upon their interaction with bacterial membranes, yet little is known about the molecular-level interactions within membranes of(More)
The N-terminal domain of fukutin-I has been implicated in the localization of the protein in the endoplasmic reticulum and Golgi Apparatus. It has been proposed to mediate this through its interaction with the thinner lipid bilayers found in these compartments. Here we have employed multiscale molecular dynamics simulations and circular dichroism(More)
The TonB-dependent transporters mediate high-affinity binding and active transport of a variety of substrates across the outer membrane of Escherichia coli. The substrates transported by these proteins are large, scarce nutrients that are unable to gain entry into the cell by passive diffusion across the complex, asymmetric bilayer that constitutes the(More)
Hia is a trimeric autotransporter found in the outer membrane of Haemphilus influenzae. The X-ray structure of Hia translocator domain revealed each monomer to consist of an α-helix connected via a loop to a 4-stranded β-sheet, thus the topology of the trimeric translocator domain is a 12-stranded β-barrel containing 3 α-helices that protrude from the mouth(More)
Dengue virus is a flavivirus responsible for millions of infections per year. Its surface contains a phospholipid bilayer, within which are embedded the envelope (E) and membrane (M) proteins, arranged with icosahedral geometry. Exposure to low pH triggers the E proteins to undergo conformational changes, which precede fusion with the host cell membrane and(More)
The bacterial outer membrane comprises two main classes of components, lipids and membrane proteins. These nonsoluble compounds are conveyed across the aqueous periplasm along specific molecular transport routes: the lipid lipopolysaccharide (LPS) is shuttled by the Lpt system, whereas outer membrane proteins (Omps) are transported by chaperones, including(More)
Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case of local ZIKV transmission and identified an ongoing cluster. Here, we report the genome sequences of ZIKV strains from two cases and find through(More)
The interactions between lipids and proteins are crucial for a range of biological processes, from the folding and stability of membrane proteins to signaling and metabolism facilitated by lipid-binding proteins. However, high-resolution structural details concerning functional lipid/protein interactions are scarce due to barriers in both experimental(More)
Molecular dynamics simulations can now routinely generate data sets of several hundreds of gigabytes in size. The ability to generate this data has become easier over recent years and the rate of data production is likely to increase rapidly in the near future. One major problem associated with this vast amount of data is how to store it in a way that it(More)
Molecular modelling and simulations have been employed to study the membranes of Gram-negative bacteria for over 20 years. Proteins native to these membranes, as well as antimicrobial peptides and drug molecules have been studied using molecular dynamics simulations in simple models of membranes, usually only comprising one lipid species. Thus,(More)