Ab initio simulations of Cu binding sites in the N-terminal region of PrP

The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)+(wat), Cu(HGGG) and the 2[Cu(HGGG)] dimer are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly's is confirmed in the case of the Cu(HGGG) system. For the more interesting 2[Cu(HGGG)] dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.Comment: 4 pages, conference proceedin

Metals in Alzheimer's disease: A combined experimental and numerical approach

Alzheimer disease is a pathology causing severe problems with memory, thinking and behavior. It accounts for the majority of dementia cases and is the sixth leading cause of death in developed countries. Unfortunately a real cure is still missing and the drug treatments today available can only reduce symptoms. It belongs to a large class of diseases, called amyloidosis, in which endogenous proteins or peptides undergo a misfolding process switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, rôle appears to be played in these processes by transition metals (mainly copper and zinc) that have been observed to be present in fairly large amounts in patient's neurological plaques. In this review we will show that the challenging problem of understanding the physico-chemical basis of protein misfolding and aggregation can be successfully investigated with a combination of modern spectroscopic techniques and advanced first principle numerical simulations. In particular, it will be shown that different metals can rival in peptide binding thus adding support to the hypothesis that metal dyshomeostasis may be relevant in the Alzheimer disease development

A simple atomistic model for the simulation of the gel phase of lipid bilayers

In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes (2x32 and 2x256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred of picoseconds for the largest system to 5--10 nanoseconds for the smallest one. We find that the bilayer remains stable even in the absence of water and neglecting Coulomb interactions in the whole range of temperatures and densities we have investigated. The extension of the region of physical parameters that we have explored has allowed us to study significant points in the phase diagram of the bilayer and to expose marked structural changes as density and temperature are varied, which are interpreted as the system passing from a crystal to a gel phase.Comment: 41 pages, 13 figure

A photon transport problem with a time-dependent point source

We consider a time-dependent problem of photon transport in an interstellar cloud with a point photon source modeled by a Dirac δ functional. The existence of a unique distributional solution to this problem is established by using the theory of continuous semigroups of operators on locally convex spaces coupled with a constructive approach for producing spaces of generalized functions

Parallel computing and molecular dynamics of biological membranes

In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on the possible programming strategies. Liquids can be very satisfactorily simulated using the "systolic" method. For more complex systems, like the biological ones at which we are ultimately interested in, the "domain decomposition" approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of elementary components of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.Comment: 4 pages LaTeX, 2 figures included, espcrc2.sty require

Constraints of T conformation of carp azide hemoglobin on Fe site structure

AbstractThe iron site structure modifications induced by the transition from the quaternary R to T structure in ferric carp azide hemoglobin have been detected from analysis of multiple scattering resonances in the XANES (X-ray absorption near edge structure) spectra. High signal-to-noise XANES spectra measured at the Frascati ‘wiggler’ synchrotron radiation facility reveal that the forces on the Fe active site, due to the transition from the R to T quaternary conformation, only induce the tilting of the porphyrin plane and probably also of the proximal histidine. The variation of the Fe-N mean distance is not detected by XANES spectroscopy and therefore it is less than 0.01 Å

Electrical properties of individual tin oxide nanowires contacted to platinum electrodes

A simple and useful experimental alternative to field-effect transistors for measuring electrical properties free electron concentration nd, electrical mobility , and conductivity in individual nanowires has been developed. A combined model involving thermionic emission and tunneling through interface states is proposed to describe the electrical conduction through the platinum-nanowire contacts, fabricated by focused ion beam techniques. Current-voltage I-V plots of single nanowires measured in both two- and four-probe configurations revealed high contact resistances and rectifying characteristics. The observed electrical behavior was modeled using an equivalent circuit constituted by a resistance placed between two back-to-back Schottky barriers, arising from the metal-semiconductor-metal M-S-M junctions. Temperature-dependent I-V measurements revealed effective Schottky barrier heights up to BE= 0.4 eV

Efeitos de doses e formas de aplicação de reguladores de crescimento em uvas sem sementes, cv. BRS Clara, em região tropical.

O objetivo deste trabalho foi avaliar o efeito do uso dos reguladores vegetais, ácido giberélico e tidiazuron, no tamanho de bagas da cultivar BRS Clara em Região Tropical. Os experimentos foram conduzidos em 2006 e 2007, na Estação Experimental de Viticultura Tropical, em Jales-SP, região noroeste do Estado de São Paulo, em plantas da cv. BRS Clara. Foram testadas diferentes concentrações de GA3 aplicadas isoladamente, combinadas com Crop Set ou tidiazuron, em aplicações únicas ou sequênciais (2 e 4 vezes). As avaliações foram feitas por ocasião da maturação das uvas, considerando-se a massa fresca dos cachos, dos engaços e das bagas, determinadas por meio de balança analítica; o comprimento e o diâmetro médio das bagas, utilizando-se de paquímetro; e o teor de sólidos solúveis (SS), por meio de refratômetro manual. Os experimentos foram conduzidos em delineamento experimental de blocos casualizados, representados por uma planta, com 15 repetições, no ano de 2006, e 10 repetições, no ano de 2007. Os dados foram submetidos à análise de variância e, para a comparação das médias dos tratamentos, foi utilizado o teste Skott Nott, ao nível de 5% de probabilidade. Observou-se que o uso dos reguladores promoveu o crescimento das bagas na cultivar BRS Clara em todos os tratamentos, diferindo da testemunh

Ultimate response dynamics achieved with gas sensors based on self-heated nanowires

Bias current applied to conductometric gas sensors consisting of individual metal oxide nanowires can be used to heat them up to the temperature necessary for sensing. This approach in combination with the good sensitivity and stability of metal-oxide nanowires, can be used to develop prototypes with low power requirements (few tens of microwatts). Here, we present new sensors devices based on this approach that display fast dynamic performance only limited by the gas-solid interaction kinetics,. © 2009

Direct correlation of crystal structure and optical properties in wurtzite/zinc-blende GaAs nanowire heterostructures

A novel method for the direct correlation at the nanoscale of structural and optical properties of single GaAs nanowires is reported. Nanowires consisting of 100% wurtzite and nanowires presenting zinc-blende/wurtzite polytypism are investigated by photoluminescence spectroscopy and transmission electron microscopy. The photoluminescence of wurtzite GaAs is consistent with a band gap of 1.5 eV. In the polytypic nanowires, it is shown that the regions that are predominantly composed of either zinc-blende or wurtzite phase show photoluminescence emission close to the bulk GaAs band gap, while regions composed of a nonperiodic superlattice of wurtzite and zinc-blende phases exhibit a redshift of the photoluminescence spectra as low as 1.455 eV. The dimensions of the quantum heterostructures are correlated with the light emission, allowing us to determine the band alignment between these two crystalline phases. Our first-principles electronic structure calculations within density functional theory, employing a hybrid-exchange functional, predict band offsets and effective masses in good agreement with experimental results