Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I-turn forming tetrapeptide and an -helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt -helical conformations stabilized by 11 successive 5 1 hydrogen bonds. In addition, a single 4 1 hydrogen bond is also observed at the N-terminus. All five Dpg residues adopt backbone torsion angles (, ) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle NCC() and the observed backbone , values. For > 106° , helices are observed, while fully extended structures are characterized by < 106° . The mean values for extended and folded conformations for the Dpg residue are 103.6° ± 1.7° and 109.9° ± 2.6° , respectively.

Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I 'beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I' beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 -> 1 hydrogen bonds. In addition, a single 4 -> 1 hydrogen bond is also observed at the N-terminus. All live Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C-alpha-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean r values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Spin populations in one-dimensional alternant spin systems: A theoretical approach

Spin-density maps, deduced from polarized neutron diffraction experiments, for both the pair and chain compounds of the system Mn2+Cu2+ have been reported recently. These results have motivated us to investigate theoretically the spin populations in such alternant mixed-spin systems. In this paper, we report our studies on the one-dimensional ferrimagnetic systems (S-A,S-B)(N) where hi is the number of AB pairs. We have considered all cases in which the spin Sri takes on allowed values in the range I to 7/2 while the spin S-B is held fixed at 1/2. The theoretical studies have been carried out on the isotropic Heisenberg model, using the density matrix renormalization group method. The effect of the magnitude of the larger spin SA On the quantum fluctuations in both A and B sublattices has been studied as a function of the system size N. We have investigated systems with both periodic and open boundary conditions, the latter with a view to understanding end-of-chain effects. The spin populations have been followed as a function of temperature as well as an applied magnetic field. High-magnetic fields are found to lead to interesting re-entrant behavior. The ratio of spin populations P-A-P-B is not sensitive to temperature at low temperatures.

Temperature dependent vibrational lifetimes in supercritical fluids near the critical point

Vibrational relaxation measurements on the CO asymmetric stretching mode (similar to 1980 cm(-1)) of tungsten hexacarbonyl (W(CO)(6)) as a function of temperature at constant density in several supercritical solvents in the vicinity of the critical point are presented. In supercritical ethane, at the critical density, there is a region above the critical temperature (Tc) in which the lifetime increases with increasing temperature. When the temperature is raised sufficiently (similar to T-c + 70 degrees C), the lifetime decreases with further increase in temperature. A recent hydrodynamic/thermodynamic theory of vibrational relaxation in supercritical fluids reproduces this behavior semiquantitatively. The temperature dependent data for fixed densities somewhat above and below the critical density is in better agreement with the theory. In fluoroform solvent at the critical density, the vibrational lifetime also initially increases with increasing temperature. However, in supercritical CO2 at the critical density, the temperature dependent vibrational lifetime decreases approximately linearly with temperature beginning almost immediately above T-c. The theory does not reproduce this behavior. A comparison between the absolute lifetimes in the three solvents and the temperature trends is made.

Universality in the fast orientational relaxation near isotropic-nematic transition

Detailed molecular dynamics simulations of Lennard-Jones ellipsoids have been carried out to investigate the emergence of criticality in the single-particle orientational relaxation near the isotropic-nematic (IN) phase transition. The simulations show a sudden appearance of a power-law behavior in the decay of the second-rank orientational relaxation as the IN transition is approached. The simulated value of the power-law exponent is 0.56, which is larger than the mean-field value (0.5) but less than the observed value (0.63) and may be due to the finite size of the simulated system. The decay of the first-rank orientational time correlation function, on the other hand, is nearly exponential but its decay becomes very slow near the isotropic-nematic transition, The zero-frequency rotational friction, calculated from the simulated angular Velocity correlation function, shows a marked increase near the IN transition.

targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis

Background: Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results: We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion: The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes.

Dynamical Transition of Water in the Grooves of DNA Duplex at Low Temperature

At low temperature (below its freezing/melting temperature), liquid water under confinement is known to exhibit anomalous dynamical features. Here we study structure and dynamics of water in the grooves of a long DNA duplex using molecular dynamics simulations with TIP5P potential at low temperature. We find signatures of a dynamical transition in both translational and orientational dynamics of water molecules in both the major and the minor grooves of a DNA duplex. The transition occurs at a slightly higher temperature (TGL ≈ 255 K) than the temperature at which the bulk water is found to undergo a dynamical transition, which for the TIP5P potential is at 247 K. Groove water, however, exhibits markedly different temperature dependence of its properties from the bulk. Entropy calculations reveal that the minor groove water is ordered even at room temperature, and the transition at T ≈ 255 K can be characterized as a strong-to-strong dynamical transition. Confinement of water in the grooves of DNA favors the formation of a low density four-coordinated state (as a consequence of enthalpy−entropy balance) that makes the liquid−liquid transition stronger. The low temperature water is characterized by pronounced tetrahedral order, as manifested in the sharp rise near 109° in the O−O−O angle distribution. We find that the Adams−Gibbs relation between configurational entropy and translational diffusion holds quite well when the two quantities are plotted together in a master plot for different region of aqueous DNA duplex (bulk, major, and minor grooves) at different temperatures. The activation energy for the transfer of water molecules between different regions of DNA is found to be weakly dependent on temperature.

Influence of cobalt doping on superconducting transition in as-grown YBCO single crystals

The role of a charge buffer layer in the superconductivity of high-T-c materials is best studied by cationic substitutions. In this work, the chain copper in YBCO single crystals is substituted by Co3+ ion and consequent effect on superconducting transition temperature (T-c) studied. The T-c is measured using non-resonant Microwave Absorption technique, which is a highly sensitive and contactless method. It is seen that T-c of as-grown crystals is considerably enhanced by cobalt doping in low concentration regime. In contrast, higher T-c is achieved in undoped crystals only after extended oxygen anneal. When dopant concentration increases beyond an optimal value, T-c decreases and the system does not show superconductivity when cobalt content is high (x > 0.5 in YBa2Cu3-xCOxO7+/-delta). This behaviour consequent to cobalt substitution is discussed with reference to the apical oxygen model. Optimal cobalt doping can be thought of as an alternative to extended oxygen anneal in as-grown crystals of YBCO.

On the cubicity of bipartite graphs

A unit cube in k-dimension (or a k-cube) is defined as the Cartesian product R-1 x R-2 x ... x R-k, where each R-i is a closed interval on the real line of the form [a(j), a(i), + 1]. The cubicity of G, denoted as cub(G), is the minimum k such that G is the intersection graph of a collection of k-cubes. Many NP-complete graph problems can be solved efficiently or have good approximation ratios in graphs of low cubicity. In most of these cases the first step is to get a low dimensional cube representation of the given graph. It is known that for graph G, cub(G) <= left perpendicular2n/3right perpendicular. Recently it has been shown that for a graph G, cub(G) >= 4(Delta + 1) In n, where n and Delta are the number of vertices and maximum degree of G, respectively. In this paper, we show that for a bipartite graph G = (A boolean OR B, E) with |A| = n(1), |B| = n2, n(1) <= n(2), and Delta' = min {Delta(A),Delta(B)}, where Delta(A) = max(a is an element of A)d(a) and Delta(B) = max(b is an element of B) d(b), d(a) and d(b) being the degree of a and b in G, respectively , cub(G) <= 2(Delta' + 2) bar left rightln n(2)bar left arrow. We also give an efficient randomized algorithm to construct the cube representation of G in 3 (Delta' + 2) bar right arrowIn n(2)bar left arrow dimension. The reader may note that in general Delta' can be much smaller than Delta.

Critical Reappraisal Of Plasticity Index Of Soils

A fundamental approach, based on Gouy-Chapman theory of double layer, has been provided to micromechanistically interpret the plasticity index of soils and their relationship with liquid limit. The relationships between plasticity index and liquid limit, developed earlier, through statistical approaches and critical state concepts, have been reexamined. The statistical analysis of extensive published data has resulted in the relationship, IP = 0.74 (wL - 8). On comparison with other relationships in vogue the proposed equation has been found to give better agreement. From the reappraisal of critical state approaches consistent with the micromechanistic interpretation, the possible range of parameters have been computed and compared with those obtained by statistical means to enhance the credibility of the proposed relationship.

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme a reductase by cytosolic proteins - real or artifact

The inhibitory effect of FeSO4-dependent cytosolic protein on microsomal HMGCoA reductase is on the enzyme activity and not an artifact of loss of the product, mevalonate, through phosphorylation, unlike that of ATP.Mg effect.

Conformational transitions in a Pro-Pro peptide on dissolution of single crystals

The peptide t-butyloxycarbonyl-α-aminoisobutyryl-L-prolyl-L-prolyl-N-methylamide has been shown to adopt an extended structure in the solid state. The Pro-Pro segment occurs in the poly-proline II conformation. On dissolution of single crystals at not, vert, similar 233°K, a single species corresponding to the all Image peptide backbone is observed by 270 MHz 1H NMR. On warming, Image to Image isomerization about the Pro-Pro bond is facilitated. Both Image (ψ not, vert, similar−50°) and Image (ψ not, vert, similar 130°) rotamers about the Pro3 Cα---CO bond are detectable in the Pro-Pro Image conformer, at low temperature. These observations demonstrate unambiguously the large differences in the solid state and solution conformations of a Pro-Pro sequence.

NMR Investigations on Di- and Tri-Azanaphthalenes Oriented in Liquid Crystals

Proton NMR spectra of 1,3-diazanaphthalene and 1,2,4-triazanaphthalene have been investigated in the nematic phase of three liquid crystals. The spectral analysis provided direct dipole-dipole couplings which have been used to derive the molecular structure. Geometry of the phenyl ring in both the molecules deviates from the regular hexagonal structure. Signs of the order parameter of the largest magnitude are opposite in liquid crystals with positive diamagetic anisotropies.

Bending Of Circular Plate On Elastic-Foundation

The governing differential equation of linear, elastic, thin, circular plate of uniform thickness, subjected to uniformly distributed load and resting on Winkler-Pasternak type foundation is solved using ``Chebyshev Polynomials''. Analysis is carried out using Lenczos' technique, both for simply supported and clamped plates. Numerical results thus obtained by perturbing the differential equation for plates without foundation are compared and are found to be in good agreement with the available results. The effect of foundation on central deflection of the plate is shown in the form of graphs.

On the eigenvalues and eigenfunctions of some integral operators

Some properties of the eigenvalues of the integral operator Kgt defined as Kτf(x) = ∫0τK(x − y) f (y) dy were studied by [1.], 554–566), with some assumptions on the kernel K(x). In this paper the eigenfunctions of the operator Kτ are shown to be continuous functions of τ under certain circumstances. Also, the results of Vittal Rao and the continuity of eigenfunctions are shown to hold for a larger class of kernels.