Role of host layer flexibility in DNA guest intercalation revealed by computer simulation of layered nanomaterials

Layered double hydroxides (LDHs) have been shown to form staged intermediate structures in experimental studies of intercalation. However, the mechanism by which staged structures are produced remains undetermined. Using molecular dynamics simulations, we show that LDHs are flexible enough to deform around bulky intercalants such as deoxyribonucleic acid (DNA). The flexibility of layered materials has previously been shown to affect the pathway by which staging occurs. We explore three possible intermediate structures which may form during intercalation of DNA into Mg2Al LDHs and study how the models differ energetically. When DNA strands are stacked directly on top of each other, the LDH system has a higher potential energy than when they are stacked in a staggered or interstratified structure. It is generally thought that staged intercalation occurs through a Daumas-Herold or a Rudorff model. We find, on average, greater diffusion coefficients for DNA strands in a Daumas-Herold configuration compared to a Rudorff model and a stage-1 structure. Our simulations provide evidence for the presence of peristaltic modes of motion within Daumas-Herold configurations. This is confirmed by spectral analysis of the thickness variation of the basal spacing. Peristaltic modes are more prominent in the Daumas-Herold structure compared to the Rudorff and stage-1 structures and support a mechanism by means of which bulky intercalated molecules such as DNA rapidly diffuse within an LDH interlayer.     

Automated molecular simulation based binding affinity calculator for ligand-bound HIV-1 proteases

The successful application of high throughput molecular simulations to determine biochemical properties would be of great importance to the biomedical community if such simulations could be turned around in a clinically relevant timescale. An important example is the determination of antiretroviral inhibitor efficacy against varying strains of HIV through calculation of drug-protein binding affinities. We describe the Binding Affinity Calculator (BAC), a tool for the automated calculation of HIV-1 protease-ligand binding affinities. The tool employs fully atomistic molecular simulations alongside the well established molecular mechanics Poisson-Boltzmann solvent accessible surface area (MMPBSA) free energy methodology to enable the calculation of the binding free energy of several ligand-protease complexes, including all nine FDA approved inhibitors of HIV-1 protease and seven of the natural substrates cleaved by the protease. This enables the efficacy of these inhibitors to be ranked across several mutant strains of the protease relative to the wildtype. BAC is a tool that utilizes the power provided by a computational grid to automate all of the stages required to compute free energies of binding: model preparation, equilibration, simulation, postprocessing, and data-marshaling around the generally widely distributed compute resources utilized. Such automation enables the molecular dynamics methodology to be used in a high throughput manner not achievable by manual methods. This paper describes the architecture and workflow management of BAC and the function of each of its components. Given adequate compute resources, BAC can yield quantitative information regarding drug resistance at the molecular level within 96 h. Such a timescale is of direct clinical relevance and can assist in decision support for the assessment of patient-specific optimal drug treatment and the subsequent response to therapy for any given genotype.     

Theory, modelling and simulation in origins of life studies

Origins of life studies represent an exciting and highly multidisciplinary research field. In this review we focus on the contributions made by theory, modelling and simulation to addressing fundamental issues in the domain and the advances these approaches have helped to make in the field. Theoretical approaches will continue to make a major impact at the "systems chemistry" level based on the analysis of the remarkable properties of nonlinear catalytic chemical reaction networks, which arise due to the auto-catalytic and cross-catalytic nature of so many of the putative processes associated with self-replication and self-reproduction. In this way, we describe inter alia nonlinear kinetic models of RNA replication within a primordial Darwinian soup, the origins of homochirality and homochiral polymerization. We then discuss state-of-the-art computationally-based molecular modelling techniques that are currently being deployed to investigate various scenarios relevant to the origins of life.     

Correcting for uranium fission in instrumental neutron activation analysis of high-uranium rocks

Failure to correct for fission products of²³⁵U is shown to result in significant errors in the measured concentrations of La, Sm, Nd, Ba, Zr, and Mo by Instrumental Neutron Activation Analysis of high uranium rocks. Measured and calculated correction factors are presented as the ratio of the fission product to parts per million by weight of uranium in the rock. Potential errors in petrogenetic interpretations of uncorrected data are outlined.     

Melledonal and melledonol,sesquiterpene esters from armillaria mellea

Isolation of two new sesquiterpene aryl esters melledonal (6) and melledonol (8) from culture broth extract of Armillaria mellea are reported. Their structures were deduced from spectral and chemical data.     

Determination of the chemical potential using energy-biased sampling

An energy-biased method to evaluate ensemble averages requiring test-particle insertion is presented. The method is based on biasing the sampling within the subdomains of the test-particle configurational space with energies smaller than a given value freely assigned. These energy wells are located via unbiased random insertion over the whole configurational space and are sampled using the so-called Hit-and-Run algorithm, which uniformly samples compact regions of any shape immersed in a space of arbitrary dimensions. Because the bias is defined in terms of the energy landscape it can be exactly corrected to obtain the unbiased distribution. The test-particle energy distribution is then combined with the Bennett relation for the evaluation of the chemical potential. We apply this protocol to a system with relatively small probability of low-energy test-particle insertion, liquid argon at high density and low temperature, and show that the energy-biased Bennett method is around five times more efficient than the standard Bennett method. A similar performance gain is observed in the reconstruction of the energy distribution.     

Self-assembly of ternary cubic, hexagonal, and lamellar mesophases using the lattice-Boltzmann kinetic method

We use a kinetic lattice-Boltzmann method to simulate the self-assembly of the cubic primitive (P), diamond (D), and gyroid (G) mesophases from an initial quench composed of oil, water, and amphiphilic particles. Here, we also report the self-assembly of the noncubic hexagonal phase and two lamellar phases, one with periodic convolutions. The periodic mesophase structures are emergent from the underlying conservation laws and quasi-molecular interactions of the lattice-Boltzmann model. We locate regions of the model's parameter space where the sequence of appearance of mesophases lamellar --> primitive --> hexagonal is in agreement with pressure jump experiments and the sequence cubic --> lamellar is in agreement with compositional variations reported in the literature. The ability of our lattice-Boltzmann model to simulate self-assembly of cubic and noncubic phases in a unified and consistent manner opens the way for further investigations into the transition pathways and kinetics of the phase transitions between these states as well as of the rheology of these phases.     

Portable X-Ray Fluorescence as a Rapid Technique for Surveying Elemental Distributions in Soil

Case studies from two sites demonstrate how concentration distributions of hazardous contaminants can be rapidly measured and visualized using portable XRF (X-ray fluorescence) coupled with geostatistical interpolation tools. In this study, lead is used as an exemplar due to its well-known detrimental effect on human health through long-term exposure. A portable Thermo Scientific NITON X-ray fluorescence (XRF) instrument was used for real-time in-situ concentration measurements, which were linked to GPS coordinates of the sampling locations. A 52 point mixed sampling density survey was performed at a site near Maynooth, Co. Kildare, and a second 58 survey undertaken at Dublin City University (DCU). At Maynooth, high concentrations of Pb (above 110 mg/kg) were found close to the site where a local canal meets a road. At the DCU site, results indicate high Pb concentrations (above 160 mg/kg) near a busy main road. Geostatistical techniques were used to generate concentration prediction and critical threshold contour surfaces for both sites. Linked with GPS coordinates for each sampling location, this technology enables the distribution of multiple elements to be mapped over wide areas in a relatively short time. Supplemental materials are available for this article. Go to the publisher's online edition of Spectroscopy Letters to view the supplemental file.     

A comparative study of the COX-1 and COX-2 isozymes bound to lipid membranes

The monotopic proteins COX-1 and -2 in dimeric form bound to lipid bilayer membranes are studied using molecular dynamics simulations within an aqueous environment. The 25-ns simulations are performed for both isozymes with arachidonic acid bound in the cyclooxygenase sites. The interactions between the enzymes and the lipids are analyzed, providing insight into the attachment mechanism of monotopic proteins to membranes. Our study reveals some key differences between the two isozymes that include the orientations at which they sit on the surface of the membranes and the depths to which they embed within the membranes. The differences in membrane association of the isozymes indicate that they may integrate distinctively with the same membrane, and/or with different membranes or their lipid components. Our results indicate that arachidonic acid can be bound in the cyclooxygenase active site in distinct catalytically competent conformations that lead to certain hydroperoxy acids; and the arachidonic acid and/or cyclooxygenase sites undergo a conformational change which makes only one subunit of each homodimer catalytically active.     

Electronic Structure Calculations Using Self-Adaptive Multiscale Voronoi Basis Functions

The multiscale self-adaptivity of Voronoi basis functions is currently proving to be useful for the simulation of complex fluid systems involving structures on a number of distinct lengthscales. In this paper, we explore the possibility of extending the use of such multiscale basis functions to the framework of density functional theoretic electronic structure computations.