Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

Background: Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results: In the present analysis, starting from C alpha positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions: Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

Inter And Intramolecular Interactions Of Porphyrins With 5,5′-Dithiobis(2-Nitrobenzoic Acid)

meso-Tetraphenylporphyrin and its metal [zinc(II) and copper(II)] derivatives form both inter and intramolecular complexes with 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). The nature of interaction is predominantly charge transfer (CT) in origin, with the porphyrin functioning as a II-donor and DTNB as an acceptor. Among the covalently linked intramolecular systems, the magnitude of CT interaction varies with the position (of one of the aryl groups of the porphyrin) to which DTNB is attached as ortho meta > para. Steady-state and time-resolved fluorescence studies revealed electron transfer to be the dominant pathway for the fluorescence quenching in these systems. Steady-state photolysis experiments probed using EPR and optical absorption studies have shown that electron transfer (from the excited singlet state of the porphyrin) to DTNB results in the formation of thiyl radical and production of free thiolate anion. It is found that the products of electrochemical reduction of covalently linked porphyrin-DTNB systems are different from those observed for the photochemical studies.

First-principles electronic structure of the delafossites ABO(2) (A=Cu, Ag, Au; B=Al, Ga, Sc, In, Y): evolution of d(10)-d(10) interactions

While bonding between d(10) atoms and ions in molecular systems has been well studied, less attention has been paid to interactions between such seemingly closed shell species in extended inorganic solids. In this contribution, we present visualizations of the electronic structures of the delafossites ABO(2) (A = Cu, Ag, Au) with particular emphasis on the nature of d(10)-d(10) interactions in the close packed plane of the coinage metal ion. We find that on going from Cu to Ag to Au, the extent of bonding between A and A increases. However, the structures (in terms of distances) of these compounds are largely determined by the strongly ionic 13,11 0 interaction and for the larger B ions Sc, In and Y, the A atoms are sufficiently well-separated that A-A bonding is almost negligible. We also analyze some interesting differences between Ag and Au, including the larger A-O covalency of the Au. The trends in electronic structure suggest that the Ag and Au compounds are not good candidate transparent conducting oxides. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

Solute-solute and solute-solvent interactions in transition metal alloys: Pt-Ti system

An isothermal section of the phase diagram for (silver + rhodium + oxygen) at T = 1173 K has been established by equilibration of samples representing twelve different compositions, and phase identification after quenching by optical and scanning electron microscopy (s.e.m.), X-ray diffraction (x.r.d.), and energy dispersive analysis of X-rays (e.d.x.), Only one ternary oxide, AgRhO2, was found to be stable and a three phase region involving Ag, AgRhO2 and Rh2O3 was identified. The thermodynamic properties of AgRhO2 were measured using a galvanic cell in the temperature range 980 K to 1320 K. Yttria-stabilized zirconia was used as the solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa was used as the reference electrode. The Gibbs free energy of formation of the ternary oxide from the elements, ΔfGo (AgRhO2), can be represented by two linear equations that join at the melting temperature of silver. In the temperature range 980 K to 1235 K, ΔfGo(AgRhO2)/(J . mol-1) = -249080 + 179.08 T/K (±120). Above the melting temperature of silver, in the temperature range 1235 K to 1320 K, ΔfGo(AgRhO2)/(J . mol-1) = -260400 + 188.24 T/K (±95). The thermodynamic properties of AgRhO2 at T = 298.15 K were evaluated from the high temperature data. The chemical potential diagram for (silver + rhodium + oxygen) at T = 1200 K was also computed on the basis of the results of this study.

Strongly magnetized cold degenerate electron gas: Mass-radius relation of the magnetized white dwarf

We consider a relativistic, degenerate electron gas at zero temperature under the influence of a strong, uniform, static magnetic field, neglecting any form of interactions. Since the density of states for the electrons changes due to the presence of the magnetic field (which gives rise to Landau quantization), the corresponding equation of state also gets modified. In order to investigate the effect of very strong magnetic field, we focus only on systems in which a maximum of either one, two, or three Landau level(s) is/are occupied. This is important since, if a very large number of Landau levels are filled, it implies a very low magnetic field strength which yields back Chandrasekhar's celebrated nonmagnetic results. The maximum number of occupied Landau levels is fixed by the correct choice of two parameters, namely, the magnetic field strength and the maximum Fermi energy of the system. We study the equations of state of these one-level, two-level, and three-level systems and compare them by taking three different maximum Fermi energies. We also find the effect of the strong magnetic field on the mass-radius relation of the underlying star composed of the gas stated above. We obtain an exciting result that it is possible to have an electron-degenerate static star, namely, magnetized white dwarfs, with a mass significantly greater than the Chandrasekhar limit in the range 2.3-2.6M(circle dot), provided it has an appropriate magnetic field strength and central density. In fact, recent observations of peculiar type Ia supernovae-SN 2006gz, SN 2007if, SN 2009dc, SN 2003fg-seem to suggest super-Chandrasekhar-mass white dwarfs with masses up to 2.4-2.8M(circle dot) as their most likely progenitors. Interestingly, our results seem to lie within these observational limits.

Role of invariant water molecules and water-mediated ionic interactions in D-xylose isomerase from Streptomyces rubiginosus

The enzyme, D-xylose isomerase (D-xylose keto-isomerase; EC 5.3.1.5) is a soluble enzyme that catalyzes the conversion of the aldo-sugar D-xylose to the keto-sugar D-xylulose. A total of 27 subunits of D-xylose isomerase from Streptomyces rubiginosus were analyzed in order to identify the invariant water molecules and their water-mediated ionic interactions. A total of 70 water molecules were found to be invariant. The structural and/or functional roles of these water molecules have been discussed. These invariant water molecules and their ionic interactions may be involved in maintaining the structural stability of the enzyme D-xylose isomerase. Fifty-eight of the 70 invariant water molecules (83%) have at least one interaction with the main chain polar atom.

Comprehensive investigations on DNa center dot center dot center dot A (D = H/F) complexes show why `sodium bonding' is not commonly observed

A comprehensive study of D-Na center dot center dot center dot A (D = H/F) complexes has been done using advanced ab initio and atoms in molecule (AIM) theoretical analyses. The correlation between electron density at bond critical point and binding energy gives a distinguishing feature for hydrogen bonding, different from the `electrostatic complexes' formed by LiD and NaD. Moreover, the LiD/NaD dimers have both linear and anti-parallel minima, as expected for electrostatic dipole-dipole interactions. The HF dimer has a quasi-linear minimum and the anti-parallel structure is a saddle point. Clearly, characterizing hydrogen bonding as `nothing but electrostatic interaction between two dipoles' is grossly in error.

Dense network of O-H ... O and C-H ... O interactions in the solid state structure of n-pentyl-2-chloro-2-deoxy-alpha-D-manno-sept 3-uloside

Single crystal X-ray structural analysis of a septanoside, namely, n-pentyl-2-chloro-2-deoxy sept-3-uloside (1) provides many finer details of the molecular structure, in addition to its preferred twist-chair conformation, namely, (TC3,4)-T-5,6 conformation. Structural analysis reveals a dense network of O-H...O, C-H...O and van der Waals interactions that stabilize interdigitized, planar bi-layer structure of the crystal lattice. (C) 2014 Elsevier Ltd. All rights reserved.

The Self-Association of Graphane Is Driven by London Dispersion and Enhanced Orbital Interactions

We investigated the nature of the cohesive energy between graphane sheets via multiple CH center dot center dot center dot HC interactions, using density functional theory (DFT) including dispersion correction (Grimmes D3 approach) computations of n]graphane sigma dimers (n = 6-73). For comparison, we also evaluated the binding between graphene sheets that display prototypical pi/pi interactions. The results were analyzed using the block-localized wave function (BLW) method, which is a variant of ab initio valence bond (VB) theory. BLW interprets the intermolecular interactions in terms of frozen interaction energy (Delta E-F) composed of electrostatic and Pauli repulsion interactions, polarization (Delta E-pol), charge-transfer interaction (Delta E-CT), and dispersion effects (Delta E-disp). The BLW analysis reveals that the cohesive energy between graphane sheets is dominated by two stabilizing effects, namely intermolecular London dispersion and two-way charge transfer energy due to the sigma CH -> sigma*(HC) interactions. The shift of the electron density around the nonpolar covalent C-H bonds involved in the intermolecular interaction decreases the C-H bond lengths uniformly by 0.001 angstrom. The Delta E-CT term, which accounts for similar to 15% of the total binding energy, results in the accumulation of electron density in the interface area between two layers. This accumulated electron density thus acts as an electronic glue for the graphane layers and constitutes an important driving force in the self-association and stability of graphane under ambient conditions. Similarly, the double faced adhesive tape style of charge transfer interactions was also observed among graphene sheets in which it accounts for similar to 18% of the total binding energy. The binding energy between graphane sheets is additive and can be expressed as a sum of CH center dot center dot center dot HC interactions, or as a function of the number of C-H bonds.

Solid state structure of p-bromo phenyl 4,5,7-tri-O-benzyl-beta-D-glycero-D-talo-septanoside and an analysis of non-covalent interactions

The solid state structure of a new seven-membered sugar oxepane derivative, namely, p-bromo phenyl 4,5,7-tri-O-benzyl-beta-D-glycero-D-talo-septanoside is discussed, as determined through single crystal X-ray structural determination and in relation to their conformational features. The molecule adopts twist-chair as the preferred conformation, with conformational descriptor (TC2,3)-T-0,1. The solid state packing of molecules is governed by a rich network of non-covalent bonding originating from O-H center dot center dot center dot O, C-H center dot center dot center dot pi, C-H center dot center dot center dot Br and aromatic pi center dot center dot center dot pi interactions that stabilize the packing of molecules in the crystal. (C) 2015 Elsevier Ltd. All rights reserved.

Graphene scavenges free radicals to synergistically enhance structural properties in a gamma-irradiated polyethylene composite through enhanced interfacial interactions

A unique strategy for scavenging free radicals in situ on exposure to gamma irradiation in polyethylene (PE) nanocomposites is presented. Blends of ultra-high molecular weight PE and linear low-density PE (PEB) and their nanocomposites with graphene (GPEB) were prepared by melt mixing to develop materials for biomedical implants. The effect of gamma irradiation on the microstructure and mechanical properties was systematically investigated. The neat blend and the nanocomposite were subjected to gamma-ray irradiation in order to improve the interfacial adhesion between PE and graphene sheets. Structural and thermal characterization revealed that irradiation induced crosslinking and increased the crystallinity of the polymer blend. The presence of graphene further enhanced the crystallinity via crosslinks between the polymer matrix and the filler on irradiation. Graphene was found to scavenge free radicals as confirmed by electron paramagnetic resonance spectroscopy. Irradiation of graphene-containing polymer composites resulted in the largest increase in modulus and hardness compared to either irradiation or addition of graphene to PEB alone. This study provides new insight into the role of graphene in polymer matrices during irradiation and suggests that irradiated graphene-polymer composites could emerge as promising materials for use as articulating surfaces in biomedical implants.

Optical-Phonon-Limited High-Field Transport in Layered Materials

An optical-phonon-limited velocity model has been employed to investigate high-field transport in a selection of layered 2-D materials for both, low-power logic switches with scaled supply voltages, and high-power, high-frequency transistors. Drain currents, effective electron velocities, and intrinsic cutoff frequencies as a function of carrier density have been predicted, thus providing a benchmark for the optical-phonon-limited high-field performance limits of these materials. The optical-phonon-limited carrier velocities for a selection of multi-layers of transition metal dichalcogenides and black phosphorus are found to be modest compared to their n-channel silicon counterparts, questioning the utility of biasing these devices in the source-injection dominated regime. h-BN, at the other end of the spectrum, is shown to be a very promising material for high-frequency, high-power devices, subject to the experimental realization of high carrier densities, primarily due to its large optical-phonon energy. Experimentally extracted saturation velocities from few-layer MoS2 devices show reasonable qualitative and quantitative agreement with the predicted values. The temperature dependence of the measured v(sat) is discussed and compared with the theoretically predicted dependence over a range of temperatures.

The interplay of localization and interactions in quantum many-body systems

Disorder and interactions both play crucial roles in quantum transport. Decades ago, Mott showed that electron-electron interactions can lead to insulating behavior in materials that conventional band theory predicts to be conducting. Soon thereafter, Anderson demonstrated that disorder can localize a quantum particle through the wave interference phenomenon of Anderson localization. Although interactions and disorder both separately induce insulating behavior, the interplay of these two ingredients is subtle and often leads to surprising behavior at the periphery of our current understanding. Modern experiments probe these phenomena in a variety of contexts (e.g. disordered superconductors, cold atoms, photonic waveguides, etc.); thus, theoretical and numerical advancements are urgently needed. In this thesis, we report progress on understanding two contexts in which the interplay of disorder and interactions is especially important.

The first is the so-called “dirty” or random boson problem. In the past decade, a strong-disorder renormalization group (SDRG) treatment by Altman, Kafri, Polkovnikov, and Refael has raised the possibility of a new unstable fixed point governing the superfluid-insulator transition in the one-dimensional dirty boson problem. This new critical behavior may take over from the weak-disorder criticality of Giamarchi and Schulz when disorder is sufficiently strong. We analytically determine the scaling of the superfluid susceptibility at the strong-disorder fixed point and connect our analysis to recent Monte Carlo simulations by Hrahsheh and Vojta. We then shift our attention to two dimensions and use a numerical implementation of the SDRG to locate the fixed point governing the superfluid-insulator transition there. We identify several universal properties of this transition, which are fully independent of the microscopic features of the disorder.

The second focus of this thesis is the interplay of localization and interactions in systems with high energy density (i.e., far from the usual low energy limit of condensed matter physics). Recent theoretical and numerical work indicates that localization can survive in this regime, provided that interactions are sufficiently weak. Stronger interactions can destroy localization, leading to a so-called many-body localization transition. This dynamical phase transition is relevant to questions of thermalization in isolated quantum systems: it separates a many-body localized phase, in which localization prevents transport and thermalization, from a conducting (“ergodic”) phase in which the usual assumptions of quantum statistical mechanics hold. Here, we present evidence that many-body localization also occurs in quasiperiodic systems that lack true disorder.

Electronic structure and phonon thermodynamics of iron alloys

Inelastic neutron scattering (INS) and nuclear-resonant inelastic x-ray scattering (NRIXS) were used to measure phonon spectra of FeV as a B2- ordered compound and as a bcc solid solution. Contrary to the behavior of ordering alloys studied to date, the phonons in the B2-ordered phase are softer than in the solid solution. Ordering increases the vibrational entropy, which stabilizes the ordered phase to higher temperatures. Ab initio calculations show that the number of electronic states at the Fermi level increases upon ordering, enhancing the screening between ions, and reducing the interatomic force constants. The effect of screening is larger at the V atomic sites than at the Fe atomic sites.

The phonon spectra of Au-rich alloys of fcc Au-Fe were also measured. The main effect on the vibrational entropy of alloying comes from a stiffening of the Au partial phonon density of states (DOS) with Fe concentration that increases the miscibility gap temperature. The magnitude of the effect is non- linear and it is reduced at higher Fe concentrations. Force constants were calculated for several compositions and show a local stiffening of Au–Au bonds close to Fe atoms, but Au–Au bonds that are farther away do not show this effect. Phonon DOS curves calculated from the force constants reproduced the experimental trends. The Au–Fe bond is soft and favors ordering, but a charge transfer from the Fe to the Au atoms stiffens the Au–Au bonds enough to favor unmixing. The stiffening is attributed to two main effects comparable in magnitude: an increase in electron density in the free-electron-like states, and stronger sd-hybridization.

INS and NRIXS measurements were performed at elevated temperatures on B2-ordered FeTi and NRIXS measurements were performed at high pressures. The high-pressure behavior is quasi- harmonic. The softening of the phonon DOS curves with temperature is strongly nonharmonic. Calculations of the force constants and Born-von Karman fits to the experimental data show that the bonds between second nearest neighbors (2nn) are much stiffer than those between 1nn, but fits to the high temperature data show that the former softens at a faster rate with temperature. The Fe–Fe bond softens more than the Ti–Ti bond. The unusual stiffness of the 2nn bond is explained by the calculated charge distribution, which is highly aspherical and localized preferentially in the t2g orbitals. Ab initio molecular dynamics (AIMD) simulations show a charge transfer from the t2g orbitals to the eg orbitals at elevated temperatures. The asphericity decreases linearly with temperature and is more severe at the Fe sites.