Computer simulation of protein systems

Ligand binding to dihydrofolate reductase (DHFR) is discussed. This is an extremely important enzyme, as it is the target of several drugs (inhibitors) which are used clinically as antibacterials, antiprotozoals and in cancer chemotherapy. DHFR catalyzes the NADPH (reduced nicotinamide adenine dinucleotide phosphate) dependent reduction of dihydrofolate to tetrahydrofolate, which is used in several pathways of purine and pyrimidine iosynthesis, including that of thymidylate. Since DNA synthesis is dependent on a continuing supply of thymidylate, a blockade of DHFR resulting in a depletion of thymidylate can lead to the cessation of growth of a rapidly proliferating cell line. DHFR exhibits a significant species to species variability in its sensitivity to various inhibitors. For example, trimethoprim, an inhibitor of DHFR, binds to bacterial DHFR's 5 orders of magnitude greater than to vertebrate DHFR's. The structural mechanics, dynamics and energetics of a family of dihydrofolate reductases are studied to rationalize the basis for the inhibitor of these enyzmes and to understand the molecular basis of the difference in the binding constants between the species. This involves investigating the conformational changes induced in the protein on binding the ligand, the internal strain imposed by the enzyme on the ligand, the restriction of fluctuations in atom positions due to binding and the consequent change in entropy

Disorder induced Coulomb gaps in graphene constrictions with different aspect ratios

We present electron transport measurements on lithographically defined and etched graphene nanoconstrictions with different aspect ratios including different lengths (L) and widths (W). A roughly length-independent disorder induced effective energy gap can be observed around the charge neutrality point. This energy gap scales inversely with the width even in regimes where the length of the constriction is smaller than its width (L<W). In very short constrictions, we observe both resonances due to localized states or charged islands and an elevated overall conductance level (0.1-1e2/h), which is strongly length-dependent in the gap region. This makes very short graphene constrictions interesting for highly transparent graphene tunneling barriers.Comment: 4 pages, 4 figure

Transport in coupled graphene-nanotube quantum devices

We report on the fabrication and characterization of all-carbon hybrid quantum devices based on graphene and single-walled carbon nanotubes. We discuss both, carbon nanotube quantum dot devices with graphene charge detectors and nanotube quantum dots with graphene leads. The devices are fabricated by chemical vapor deposition growth of carbon nanotubes and subsequent structuring of mechanically exfoliated graphene. We study the detection of individual charging events in the carbon nanotube quantum dot by a nearby graphene nanoribbon and show that they lead to changes of up to 20% of the conductance maxima in the graphene nanoribbon acting as a good performing charge detector. Moreover, we discuss an electrically coupled graphene-nanotube junction, which exhibits a tunneling barrier with tunneling rates in the low GHz regime. This allows to observe Coulomb blockade on a carbon nanotube quantum dot with graphene source and drain leads

To integrate or to segregate food crop and energy crop cultivation at the landscape scale? Perspectives on biodiversity conservation in agriculture in Europe

Biodiversity is severely declining in intensively managed agriculture worldwide. In response, land-management strategies for biodiversity conservation on farmland are in debate, namely ecological intensification and land sparing vs. land sharing. In parallel, there is a recent food vs. energy debate stimulated by an increasing competition for land resources. Despite clear overlaps between these two debates, they were rarely connected in previous research. This paper aims to stimulate a discussion by providing a contextual link between biodiversity conservation strategies and options for future energy crop deployment. Therefore, nine conceptual land-use scenarios are developed, and then, the potential biodiversity implications are discussed based on the findings from past and ongoing research. These scenarios include the integration and segregation of both food and energy crops on lands with a range of productivity and suitability for agricultural production. We assume that the clear segregation between food crops on productive land and energy crops on marginal land is less likely to be a solution of mitigating the problems related to the biodiversity decline, especially in the European agricultural landscape context. In contrast, the integration of food and energy crop production systems at the farm to landscape scale has greater potential for ecological intensification, although conflicts with traditional nature conservation targets may arise. We conclude that broadening the perspectives of biodiversity conservation in agriculture is crucial, and the inclusion of energy crop production into the recent debates on biodiversity conservation strategies is helpful

Consequential life cycle assessment of biogas, biofuel and biomass energy options within an arable crop rotation

Feed in tariffs (FiTs) and renewable heat incentives (RHIs) are driving a rapid expansion in anaerobic digestion (AD) coupled with combined heat and power (CHP) plants in the UK. Farm models were combined with consequential life cycle assessment (CLCA) to assess the net environmental balance of representative biogas, biofuel and biomass scenarios on a large arable farm, capturing crop rotation and digestate nutrient cycling effects. All bioenergy options led to avoided fossil resource depletion. Global warming potential (GWP) balances ranged from -1732kgCO(2)eMg(-1) dry matter (DM) for pig slurry AD feedstock after accounting for avoided slurry storage to +2251kgCO(2)eMg(-1) DM for oilseed rape biodiesel feedstock after attributing indirect land use change (iLUC) to displaced food production. Maize monoculture for AD led to net GWP increases via iLUC, but optimized integration of maize into an arable rotation resulted in negligible food crop displacement and iLUC. However, even under best-case assumptions such as full use of heat output from AD-CHP, crop-biogas achieved low GWP reductions per hectare compared with Miscanthus heating pellets under default estimates of iLUC. Ecosystem services (ES) assessment highlighted soil and water quality risks for maize cultivation. All bioenergy crop options led to net increases in eutrophication after displaced food production was accounted for. The environmental balance of AD is sensitive to design and management factors such as digestate storage and application techniques, which are not well regulated in the UK. Currently, FiT payments are not dependent on compliance with sustainability criteria. We conclude that CLCA and ES effects should be integrated into sustainability criteria for FiTs and RHIs, to direct public money towards resource-efficient renewable energy options that achieve genuine climate protection without degrading soil, air or water qualit

A robust nanoscale experimental quantification of fracture energy in a bilayer material system

Accurate measurement of interfacial properties is critical any time two materials are bonded—in composites, tooth crowns, or when biomaterials are attached to the human body. Yet, in spite of this importance, reliable methods to measure interfacial properties between dissimilar materials remain elusive. Here we present an experimental approach to quantify the interfacial fracture energy Γ[subscript i] that also provides unique mechanistic insight into the interfacial debonding mechanism at the nanoscale. This approach involves deposition of an additional chromium layer (superlayer) onto a bonded system, where interface debonding is initiated by the residual tensile stress in the superlayer, and where the interface can be separated in a controlled manner and captured in situ. Contrary to earlier methods, our approach allows the entire bonded system to remain in an elastic range during the debonding process, such that Γ[subscript i] can be measured accurately. We validate the method by showing that moisture has a degrading effect on the bonding between epoxy and silica, a technologically important interface. Combining in situ through scanning electron microscope images with molecular simulation, we find that the interfacial debonding mechanism is hierarchical in nature, which is initiated by the detachment of polymer chains, and that the three-dimensional covalent network of the epoxy-based polymer may directly influence water accumulation, leading to the reduction of Γ[subscript i] under presence of moisture. The results may enable us to design more durable concrete composites that could be used to innovate transportation systems, create more durable buildings and bridges, and build resilient infrastructure.National Science Foundation (U.S.) (Grant CMS-0856325