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Sample records for residual two-body interaction

  1. Separable approximations of two-body interactions

    NASA Astrophysics Data System (ADS)

    Haidenbauer, J.; Plessas, W.

    1983-01-01

    We perform a critical discussion of the efficiency of the Ernst-Shakin-Thaler method for a separable approximation of arbitrary two-body interactions by a careful examination of separable 3S1-3D1 N-N potentials that were constructed via this method by Pieper. Not only the on-shell properties of these potentials are considered, but also a comparison is made of their off-shell characteristics relative to the Reid soft-core potential. We point out a peculiarity in Pieper's application of the Ernst-Shakin-Thaler method, which leads to a resonant-like behavior of his potential 3SD1D. It is indicated where care has to be taken in order to circumvent drawbacks inherent in the Ernst-Shakin-Thaler separable approximation scheme. NUCLEAR REACTIONS Critical discussion of the Ernst-Shakin-Thaler separable approximation method. Pieper's separable N-N potentials examined on shell and off shell.

  2. Multinucleon Ejection Model for Two Body Current Neutrino Interactions

    SciTech Connect

    Sobczyk, Jan T.; /Fermilab

    2012-06-01

    A model is proposed to describe nucleons ejected from a nucleus as a result of two-body-current neutrino interactions. The model can be easily implemented in Monte Carlo neutrino event generators. Various possibilities to measure the two-body-current contribution are discussed. The model can help identify genuine charge current quasielastic events and allow for a better determination of the systematic error on neutrino energy reconstruction in neutrino oscillation experiments.

  3. Unsteady Aerodynamic Interaction between Two Bodies at Hypersonic Speed

    NASA Astrophysics Data System (ADS)

    Ozawa, Hiroshi; Kitamura, Keiichi; Hanai, Katsuhisa; Mori, Koichi; Nakamura, Yoshiaki

    This paper presents experimental results of unsteady aerodynamic interactions including Shock/Shock Interaction (SSI) and Shock/Boundary Layer Interaction (SBLI) between two bodies at hypersonic speed. These interactions can be seen in space vehicles consisting of multi-bodies, such as a TSTO, or at a scramjet engine inlet. The present study considers the effect of a flat plate below the SSI where a boundary-layer is developed on the plate surface. More specifically, the interacted flow for a combination of a flat plate (FP) and a hemi-circular cylinder (HCC) is examined at a hypersonic speed (M∞=8.1) the distributions of surface pressure and heat transfer rate are measured. To obtain various SSI patterns, the clearance between two bodies (FP and HCC) is changed. Results show that unsteadiness at the SSI point causes a feedback loop between the two bodies; a jet flow impinges on the FP, the effect of which propagates upstream where the jet impinges on the FP, and the aerodynamic and aerothermodynamic loads reach their maxima. Finally, we found that the feedback loop can be destroyed by installing a fence on the FP to reduce unsteadiness of flow field.

  4. Electromagnetic interactions for the two-body spectator equations

    SciTech Connect

    J. Adam; Franz Gross; J.W. Van Orden

    1997-10-01

    This paper presents a new non-associative algebra which is used to (1) show how the spectator (or Gross) two-body equations and electromagnetic currents can be formally derived from the Bethe-Salpeter equation and currents if both are treated to all orders, (2) obtain explicit expressions for the Gross two-body electromagnetic currents valid to any order, and (3) prove that the currents so derived are exactly gauge invariant when truncated consistently to any finite order. In addition to presenting these new results, this work complements and extends previous treatments based largely on the analysis of sums of Feynman diagrams.

  5. Proton-neutron interacting boson model under random two-body interactions

    SciTech Connect

    Yoshida, N.; Zhao, Y. M.; Arima, A.

    2009-12-15

    The low-lying states of sd-boson systems in the presence of random two-body interactions are studied in the proton-neutron interacting boson model (IBM-2). The predominance of spin-zero ground states is confirmed, and a very prominent maximum F-spin dominance in ground states is found. It turns out that the requirement of random interactions with F-spin conservation intensifies the above predominance. Collective motion in the low-lying states is discussed.

  6. Statistical mechanics of nucleosome ordering by chromatin-structure-induced two-body interactions.

    PubMed

    Chereji, Răzvan V; Tolkunov, Denis; Locke, George; Morozov, Alexandre V

    2011-05-01

    One-dimensional arrays of nucleosomes (DNA-bound histone octamers separated by stretches of linker DNA) fold into higher-order chromatin structures which ultimately make up eukaryotic chromosomes. Chromatin structure formation leads to 10-11 base pair (bp) discretization of linker lengths caused by the smaller free energy cost of packaging nucleosomes into regular chromatin fibers if their rotational setting (defined by the DNA helical twist) is conserved. We describe nucleosome positions along the fiber using a thermodynamic model of finite-size particles with both intrinsic histone-DNA interactions and an effective two-body potential. We infer one- and two-body energies directly from high-throughput maps of nucleosome positions. We show that higher-order chromatin structure helps explains in vitro and in vivo nucleosome ordering in transcribed regions, and plays a leading role in establishing well-known 10-11 bp genome-wide periodicity of nucleosome positions.

  7. Statistical mechanics of nucleosome ordering by chromatin-structure-induced two-body interactions

    NASA Astrophysics Data System (ADS)

    Chereji, Răzvan V.; Tolkunov, Denis; Locke, George; Morozov, Alexandre V.

    2011-05-01

    One-dimensional arrays of nucleosomes (DNA-bound histone octamers separated by stretches of linker DNA) fold into higher-order chromatin structures which ultimately make up eukaryotic chromosomes. Chromatin structure formation leads to 10-11 base pair (bp) discretization of linker lengths caused by the smaller free energy cost of packaging nucleosomes into regular chromatin fibers if their rotational setting (defined by the DNA helical twist) is conserved. We describe nucleosome positions along the fiber using a thermodynamic model of finite-size particles with both intrinsic histone-DNA interactions and an effective two-body potential. We infer one- and two-body energies directly from high-throughput maps of nucleosome positions. We show that higher-order chromatin structure helps explains in vitro and in vivo nucleosome ordering in transcribed regions, and plays a leading role in establishing well-known 10-11 bp genome-wide periodicity of nucleosome positions.

  8. Effective quantum-memory Hamiltonian from local two-body interactions

    NASA Astrophysics Data System (ADS)

    Hutter, Adrian; Pedrocchi, Fabio L.; Wootton, James R.; Loss, Daniel

    2014-07-01

    In Phys. Rev. A 88, 062313 (2013), 10.1103/PhysRevA.88.062313 we proposed and studied a model for a self-correcting quantum memory in which the energetic cost for introducing a defect in the memory grows without bounds as a function of system size. This positive behavior is due to attractive long-range interactions mediated by a bosonic field to which the memory is coupled. The crucial ingredients for the implementation of such a memory are the physical realization of the bosonic field as well as local five-body interactions between the stabilizer operators of the memory and the bosonic field. Here, we show that both of these ingredients appear in a low-energy effective theory of a Hamiltonian that involves only two-body interactions between neighboring spins. In particular, we consider the low-energy, long-wavelength excitations of an ordered Heisenberg ferromagnet (magnons) as a realization of the bosonic field. Furthermore, we present perturbative gadgets for generating the required five-spin operators. Our Hamiltonian involving only local two-body interactions is thus expected to exhibit self-correcting properties as long as the noise affecting it is in the regime where the effective low-energy description remains valid.

  9. The role of two body interaction on the broadening of a Förster resonance

    NASA Astrophysics Data System (ADS)

    Kondo, Jorge; Goncalves, Luis; Tallant, Jonathan; Booth, Donald; Shaffer, James; Marcassa, Luis

    2015-05-01

    Since the early days of ultracold Rydberg atom physics, many-body effects in ultracold trapped alkali gases has been of central interest. The first experiments in this field involved the study of Förster resonances as a function of atomic density. We present a study of a dc electric field tuned Förster resonance involving 37D state Rb atoms in a high density atomic sample held in an optical dipole trap. Our results show that as the atomic density increases, the resonance linewidth increases until the resonance peaks merge. Simultaneously, we measure the 39P state population which is produced through interactions between 37D atoms. It is shown that the 39P population depends quadratically on the total Rydberg 37D atomic population. A theoretical model that takes into account the multilevel character of the interaction and Rydberg atom blockade process using only pair interactions was implemented to explain the results. The comparison between the experimental data and the model is very good, suggesting that the Föster resonance process is dominate by two-body interaction. This work was supported by Fapesp, NSF and INCT-IQ.

  10. Microscopy of the interacting Harper-Hofstadter model in the two-body limit

    NASA Astrophysics Data System (ADS)

    Tai, M. Eric; Lukin, Alexander; Rispoli, Matthew; Schittko, Robert; Menke, Tim; Dan Borgnia; Preiss, Philipp M.; Grusdt, Fabian; Kaufman, Adam M.; Greiner, Markus

    2017-06-01

    The interplay between magnetic fields and interacting particles can lead to exotic phases of matter that exhibit topological order and high degrees of spatial entanglement. Although these phases were discovered in a solid-state setting, recent innovations in systems of ultracold neutral atoms—uncharged atoms that do not naturally experience a Lorentz force—allow the synthesis of artificial magnetic, or gauge, fields. This experimental platform holds promise for exploring exotic physics in fractional quantum Hall systems, owing to the microscopic control and precision that is achievable in cold-atom systems. However, so far these experiments have mostly explored the regime of weak interactions, which precludes access to correlated many-body states. Here, through microscopic atomic control and detection, we demonstrate the controlled incorporation of strong interactions into a two-body system with a chiral band structure. We observe and explain the way in which interparticle interactions induce chirality in the propagation dynamics of particles in a ladder-like, real-space lattice governed by the interacting Harper-Hofstadter model, which describes lattice-confined, coherently mobile particles in the presence of a magnetic field. We use a bottom-up strategy to prepare interacting chiral quantum states, thus circumventing the challenges of a top-down approach that begins with a many-body system, the size of which can hinder the preparation of controlled states. Our experimental platform combines all of the necessary components for investigating highly entangled topological states, and our observations provide a benchmark for future experiments in the fractional quantum Hall regime.

  11. Microscopy of the interacting Harper-Hofstadter model in the two-body limit.

    PubMed

    Tai, M Eric; Lukin, Alexander; Rispoli, Matthew; Schittko, Robert; Menke, Tim; Dan Borgnia; Preiss, Philipp M; Grusdt, Fabian; Kaufman, Adam M; Greiner, Markus

    2017-06-21

    The interplay between magnetic fields and interacting particles can lead to exotic phases of matter that exhibit topological order and high degrees of spatial entanglement. Although these phases were discovered in a solid-state setting, recent innovations in systems of ultracold neutral atoms-uncharged atoms that do not naturally experience a Lorentz force-allow the synthesis of artificial magnetic, or gauge, fields. This experimental platform holds promise for exploring exotic physics in fractional quantum Hall systems, owing to the microscopic control and precision that is achievable in cold-atom systems. However, so far these experiments have mostly explored the regime of weak interactions, which precludes access to correlated many-body states. Here, through microscopic atomic control and detection, we demonstrate the controlled incorporation of strong interactions into a two-body system with a chiral band structure. We observe and explain the way in which interparticle interactions induce chirality in the propagation dynamics of particles in a ladder-like, real-space lattice governed by the interacting Harper-Hofstadter model, which describes lattice-confined, coherently mobile particles in the presence of a magnetic field. We use a bottom-up strategy to prepare interacting chiral quantum states, thus circumventing the challenges of a top-down approach that begins with a many-body system, the size of which can hinder the preparation of controlled states. Our experimental platform combines all of the necessary components for investigating highly entangled topological states, and our observations provide a benchmark for future experiments in the fractional quantum Hall regime.

  12. Potential harmonics expansion method for trapped interacting bosons: Inclusion of two-body correlation

    SciTech Connect

    Das, T.K.; Chakrabarti, B.

    2004-12-01

    We study a system of A identical interacting bosons trapped by an external field by solving ab initio the many-body Schroedinger equation. A complete solution by using, for example, the traditional hyperspherical harmonics (HH) basis develops serious practical problems due to the large degeneracy of HH basis. Symmetrization of the wave function, calculation of the matrix elements, etc., become an immensely formidable task as A increases. Instead of the HH basis, here we use a new basis, called 'potential harmonics' (PH) basis, which is a subset of HH basis. We assume that the contribution to the orbital and grand orbital [in 3(A-1)-dimensional space of the reduced motion] quantum numbers comes only from the interacting pair. This implies inclusion of two-body correlations only and disregard of all higher-body correlations. Such an assumption is ideally suited for the Bose-Einstein condensate (BEC), which is required, for experimental realization of BEC, to be extremely dilute. Hence three and higher-body collisions are almost totally absent. Unlike the (3A-4) hyperspherical variables in HH basis, the PH basis involves only three active variables, corresponding to three quantum numbers--the orbital l, azimuthal m, and the grand orbital 2K+l quantum numbers for any arbitrary A. It drastically reduces the number of coupled equations and calculation of the potential matrix becomes tremendously simplified, as it involves integrals over only three variables for any A. One can easily incorporate realistic atom-atom interactions in a straightforward manner. We study the ground and excited state properties of the condensate for both attractive and repulsive interactions for various particle number. The ground state properties are compared with those calculated from the Gross-Pitaevskii equation. We notice that our many-body results converge towards the mean field results as the particle number increases.

  13. The two-body interaction potential in the STF tensor formalism: an application to binary asteroids

    NASA Astrophysics Data System (ADS)

    Compère, A.; Lemaître, A.

    2014-08-01

    The symmetric trace free (STF) tensor formalism, developed by Hartmann et al. (Celest Mech Dyn Astron 60:139-159. doi: 10.1007/BF00693097, 1994), is a nice tool, not much used in Celestial Mechanics. It is fully equivalent to the usual spherical harmonics but permits more elegant and compact formulations. The coupling between the gravitational fields of extended bodies with this formalism has been used in Mathis and Le Poncin-Lafitte (Astron Astrophys 497:889-910. doi: 10.1051/0004-6361/20079054, 2009) for binary stars or planetary systems, but not yet applied to binary asteroids. However, binary asteroids are common in the Solar System and usually their study requires a full two rigid body approach. The formulation of the two-body interaction potential in the STF formalism in the full two rigid body problem is detailed and completed in this article. An application to the binary asteroid (66391) 1999 KW4 is presented with a comparison of our results with other results of the literature for validation.

  14. Program in C for studying characteristic properties of two-body interactions in the framework of spectral distribution theory

    NASA Astrophysics Data System (ADS)

    Launey, K. D.; Sarbadhicary, S.; Dytrych, T.; Draayer, J. P.

    2014-01-01

    We present a program in C that employs spectral distribution theory for studies of characteristic properties of a many-particle quantum-mechanical system and the underlying few-body interaction. In particular, the program focuses on two-body nuclear interactions given in a JT-coupled harmonic oscillator basis and calculates correlation coefficients, a measure of similarity of any two interactions, as well as Hilbert-Schmidt norms specifying interaction strengths. An important feature of the program is its ability to identify the monopole part (centroid) of a 2-body interaction, as well as its 'density-dependent' one-body and two-body part, thereby providing key information on the evolution of shell gaps and binding energies for larger nuclear systems. As additional features, we provide statistical measures for 'density-dependent' interactions, as well as a mechanism to express an interaction in terms of two other interactions. This, in turn, allows one to identify, e.g., established features of the nuclear interaction (such as pairing correlations) within a general Hamiltonian. The program handles the radial degeneracy for 'density-dependent' one-body interactions and together with an efficient linked list data structure, facilitates studies of nuclear interactions in large model spaces that go beyond valence-shell applications.

  15. Two-body state with p -wave interaction in a one-dimensional waveguide under transversely anisotropic confinement

    NASA Astrophysics Data System (ADS)

    Gao, Tian-You; Peng, Shi-Guo; Jiang, Kaijun

    2015-04-01

    We theoretically study two atoms with p -wave interaction in a one-dimensional waveguide, investigating how the transverse anisotropy of the confinement affects the two-body state, especially the properties of the resonance. For a bound-state solution, we find there are a total of three two-body bound states due to the richness of the orbital magnetic quantum number of the p -wave interaction, while only one bound state is supported by the s -wave interaction. Two of them become nondegenerate due to the breaking of the rotation symmetry under a transversely anisotropic confinement. For a scattering solution, the effective one-dimensional scattering amplitude and scattering length are derived. We find the position of the p -wave confinement-induced resonance shifts apparently versus the transverse anisotropy. In addition, a two-channel mechanism for the confinement-induced resonance in a one-dimensional waveguide is generalized to the p -wave interaction, which was previously proposed only for the s -wave interaction. All our calculations are based on the parametrization of the 40K-atom experiments and can thus be confirmed in future experiments.

  16. Relation between the change of density of states and the shape of the potential in two-body interactions

    NASA Astrophysics Data System (ADS)

    Gao, Bo

    2017-04-01

    We derive a general relation in two-body scattering theory that more directly relates the change of density of states (DDOS) due to interaction to the shape of the potential. The relation allows us to infer certain global properties of the DDOS from the global properties of the potential. In particular, we show that DDOS is negative at all energies and for all partial waves, for potentials that are more repulsive than +1 /r2 everywhere. This behavior represents a different class of global properties of DDOS from that described by the Levinson's theorem.

  17. Analytic solutions for Wheeler-Feynman interaction: Two bodies in straight-line motion

    NASA Astrophysics Data System (ADS)

    Stephas, Paul

    1992-02-01

    Analytic solutions are obtained for two point particles with any total energy that have charges of like sign and whose motions are confined to one dimension. These solutions are obtained by explicitly deriving the conserved quantities associated with Wheeler-Feynman interactions into forms that do not contain integrals but, rather, contain ``partial contributions'' to the momenta and potentials of particle two. The resulting conserved energy, momentum, and Lorentz momentum equations are separated in time to yield one set of equations with variables t1 and t2- (retarded) and another set with variables t1 and t1+ (advanced). These are solved to obtain auxiliary solutions x1r(t1) and x1a(t1), which are then combined for the case m1 = m2 to give the actual world lines x1(t1) and x2(t2). Comparison is made with a previous computer-generated exact solution for the same interaction and energy; good qualitative agreement is found, although some quantitative differences persist.

  18. Solution of two-body relativistic bound state equations with confining plus Coulomb interactions

    NASA Technical Reports Server (NTRS)

    Maung, Khin Maung; Kahana, David E.; Norbury, John W.

    1992-01-01

    Studies of meson spectroscopy have often employed a nonrelativistic Coulomb plus Linear Confining potential in position space. However, because the quarks in mesons move at an appreciable fraction of the speed of light, it is necessary to use a relativistic treatment of the bound state problem. Such a treatment is most easily carried out in momentum space. However, the position space Linear and Coulomb potentials lead to singular kernels in momentum space. Using a subtraction procedure we show how to remove these singularities exactly and thereby solve the Schroedinger equation in momentum space for all partial waves. Furthermore, we generalize the Linear and Coulomb potentials to relativistic kernels in four dimensional momentum space. Again we use a subtraction procedure to remove the relativistic singularities exactly for all partial waves. This enables us to solve three dimensional reductions of the Bethe-Salpeter equation. We solve six such equations for Coulomb plus Confining interactions for all partial waves.

  19. Repulsive bound-atom pairs in an optical lattice with two-body interaction of nearest neighbors

    SciTech Connect

    Wang, Y.-M.; Liang, J.-Q.

    2010-04-15

    Repulsively interacting particles in a periodic potential can form bound composite objects with long lifetimes, as has been observed experimentally [Winkler et al., Nature (London) 441, 853 (2006)]. In this paper, a complete two-particle solution of one-dimensional periodical potential was derived in a strong interaction regime, where the on-site approximation of a two-body interaction in the Bose-Hubbard model (BHM) is extended to include the interaction of nearest neighbors, which results in atom-pair hopping. The energy spectrum of the bound pair is drastically reshaped due to the pair-hopping term, and complex eigenenergy corresponding to metastable states is also found that has not been discovered in the usual BHM. When the absolute value of a center-of-mass quasimomentum wave vector is greater than a critical value (|K|>K{sub c}), two bound-pair solutions are found. Furthermore, the spatial and momentum distributions of the bound pair displays a crossover from dark to bright soliton-like solutions in the extended BHM. Our results reduce to that of the usual BHM in the weak interaction case.

  20. Use of Two-Body Correlated Basis Functions with van der Waals Interaction to Study the Shape-Independent Approximation for a Large Number of Trapped Interacting Bosons

    NASA Astrophysics Data System (ADS)

    Lekala, M. L.; Chakrabarti, B.; Das, T. K.; Rampho, G. J.; Sofianos, S. A.; Adam, R. M.; Haldar, S. K.

    2017-01-01

    We study the ground-state and the low-lying excitations of a trapped Bose gas in an isotropic harmonic potential for very small (˜ 3) to very large (˜ 10^7 ) particle numbers. We use the two-body correlated basis functions and the shape-dependent van der Waals interaction in our many-body calculations. We present an exhaustive study of the effect of inter-atomic correlations and the accuracy of the mean-field equations considering a wide range of particle numbers. We calculate the ground-state energy and the one-body density for different values of the van der Waals parameter C6 . We compare our results with those of the modified Gross-Pitaevskii results, the correlated Hartree hypernetted-chain equations (which also utilize the two-body correlated basis functions), as well as of the diffusion Monte Carlo for hard sphere interactions. We observe the effect of the attractive tail of the van der Waals potential in the calculations of the one-body density over the truly repulsive zero-range potential as used in the Gross-Pitaevskii equation and discuss the finite-size effects. We also present the low-lying collective excitations which are well described by a hydrodynamic model in the large particle limit.

  1. Evidence for the two-body nature of the E1 transition operator in the sdf-interacting boson model

    NASA Astrophysics Data System (ADS)

    Barfield, A. F.; von Brentano, P.; Dewald, A.; Zell, K. O.; Zamfir, N. V.; Bucurescu, D.; Ivaşcu, M.; Scholten, O.

    1989-03-01

    Two new absolute transition rates are reported for the nucleus144Sm following an ( α, α') Coulomb excitation study. They are B(E3; 3-→ 0+)=(38±3) W.u. and B(E1;3- → 2+)=(2.8±0.4)×10-3 W.u. This large E1 matrix element, along with the previously known B(E1; 1- →+) value support the interpretation of the 1- state in this nucleus as 2-phonon 2+ × 3- excitation. In the frame of the IBM-1 + f-boson model we show the need for a two-body term in the E1 transition operator. Estimates for the strengths of the one and two-body parts of the E1 transition operator are obtained from these experimental data.

  2. Applications of Two-Body Dirac Equations to the Meson Spectrum with Three Versus Two Covariant Interactions, SU(3) Mixing

    NASA Astrophysics Data System (ADS)

    Schiermeyer, James; Crater, Horace

    2012-03-01

    In a previous work Crater and Van Alstine applied the Two Body Dirac equations of constraint dynamics to quark-antiquark bound states using a relativistic extention of the Adler-Piran potential in which the transformation properties of the quark-antiquark potentials were limited to a scalar and an electromagnetic-like four vector, with the former accounting for the confining aspects of the overall potential, and the latter the short range portion. The static Adler-Piran potential was first given an invariant form and then apportioned between those two different types of potentials. Here we make a change in this apportionment that leads to a substantial improvement in the resultant spectroscopy by including a time-like confining vector potential over and above the scalar confining one and the electromagnetic-like vector potential. Our fit includes 19 more mesons than the earlier results and we modify the scalar portion of the potential in such a way that allows this formalism to account for the isoscalar mesons η and η' not included in the previous work.

  3. Gravitational self-force corrections to two-body tidal interactions and the effective one-body formalism

    NASA Astrophysics Data System (ADS)

    Bini, Donato; Damour, Thibault

    2014-12-01

    Tidal interactions have a significant influence on the late dynamics of compact binary systems, which constitute the prime targets of the upcoming network of gravitational-wave detectors. We refine the theoretical description of tidal interactions (hitherto known only to the second post-Newtonian level) by extending our recently developed analytic self-force formalism, for extreme-mass-ratio binary systems, to the computation of several tidal invariants. Specifically, we compute, to linear order in the mass ratio and to the 7.5th post-Newtonian order, the following tidal invariants: the square and the cube of the gravitoelectric quadrupolar tidal tensor, the square of the gravitomagnetic quadrupolar tidal tensor, and the square of the gravitoelectric octupolar tidal tensor. Our high-accuracy analytic results are compared to recent numerical self-force tidal data by Dolan et al. [arXiv:1406.4890 [Phys. Rev. D (to be published)] ], and, notably, provide an analytic understanding of the light ring asymptotic behavior found by them. We transcribe our kinematical tidal-invariant results in the more dynamically significant effective one-body description of the tidal interaction energy. By combining, in a synergetic manner, analytical and numerical results, we provide simple, accurate analytic representations of the global, strong-field behavior of the gravitoelectric quadrupolar tidal factor. A striking finding is that the linear-in-mass-ratio piece in the latter tidal factor changes sign in the strong-field domain, to become negative (while its previously known second post-Newtonian approximant was always positive). We, however, argue that this will be more than compensated by a probable fast growth, in the strong-field domain, of the nonlinear-in-mass-ratio contributions in the tidal factor.

  4. Effect of the band structure in a rigorous two-body model with long-range interactions in 1D optical lattices

    NASA Astrophysics Data System (ADS)

    Kristensen, Tom; Simoni, Andrea; Launay, Jean-Michel

    2016-05-01

    We compute scattering and bound state properties for two ultracold molecules in a pure 1D optical lattice. We introduce reference functions with complex quasi-momentum that naturally account for the effect of excited energy bands. Our exact results for a short-range interaction are first compared with the simplest version of the standard Bose-Hubbard (BH) model. Such comparison allows us to highlight the effect of the excited bands, of the non-on-site interaction and of tunneling with distant neighbor, that are not taken into account in the BH model. The effective interaction can depend strongly on the particle quasi-momenta and can present a resonant behavior even in a deep lattice. As a second step, we study scattering of two polar particles in the optical lattice. Peculiar Wigner threshold laws stem from the interplay of the long range dipolar interaction and the presence of the energy bands. We finally assess the validity of an extended Bose-Hubbard model for dipolar gases based on our exact two-body calculations. This work was supported by the Agence Nationale de la Recherche (Contract No. ANR-12-BS04-0020-01).

  5. Two- and quasi-two-body strange particle final state production in. pi. /sup +/p interactions at low to intermediate energies

    SciTech Connect

    Hanson, P.

    1982-10-01

    The two and quasi-two body final states ..sigma../sup +/K/sup +/, ..sigma../sup +/K* (892)/sup +/, ..sigma..*(1385)/sup +/K/sup +/, ..sigma..(1385)/sup +/K*(892)/sup +/ produced by neutral strangeness exchange in ..pi../sup +/p interactions are studied using our own 1-3 GeV/c data, comprising the 14 incident momenta of a two million picture bubble chamber experiment, in combination with the world data on the same and related channels. Because low energy resonance formation is not strongly coupled to the ..sigma..,..sigma..* production channels, at very modest incident momenta their dominant features are seen to be understandable in terms of high energy hypercharge exchange phenomenology. We find that Regge models fitted to data in the 10 to 20 GeV/c range adequately describe the ..sigma.. and ..sigma..* channels down to within a few hundred MeV/c of threshold and out to large center of mass scattering angles, and that over the range of the available world data weak exchange degeneracy expectations for these reactions are at least qualitatively successful. We observe that the SU(2), SU(3) flavor symmetries successfully describe these hypercharge exchange processes and relate them to charge exchange via sum rules and equalities expressing flavor independence of the strong interaction; in particular, we derive and test on the available world data a mass broken SU(3) sum rule for ..pi../sup +/p ..-->.. K/sup +/..sigma../sup +/, ..pi../sup -/p ..-->.. K/sup 0/..lambda.., K/sup -/p ..-->.. anti K/sup 0/n and test over a wider range of momenta than before an earlier expression relating ..sigma..* and ..delta.. production. We also find at least qualitative agreement between quark model predictions for forward hypercharge exchange and the data, and we find that 90/sup 0/ hypercharge exchange cross sections also conform to the expectations of the quark constituent picture for hadrons.

  6. Applications of two-body Dirac equations to the meson spectrum with three versus two covariant interactions, SU(3) mixing, and comparison to a quasipotential approach

    NASA Astrophysics Data System (ADS)

    Crater, Horace W.; Schiermeyer, James

    2010-11-01

    In a previous paper, Crater and Van Alstine applied the two-body Dirac equations of constraint dynamics to quark-antiquark bound states using a relativistic extention of the Adler-Piran potential and compared their spectral results to those from other approaches which also considered meson spectroscopy as a whole and not in parts. In this paper, we explore in more detail the differences and similarities in an important subset of those approaches, the quasipotential approach. In the earlier paper, the transformation properties of the quark-antiquark potentials were limited to a scalar and an electromagnetic-like four-vector, with the former accounting for the confining aspects of the overall potential, and the latter the short range portion. The static Adler-Piran potential was first given an invariant form and then apportioned between those two different types of potentials. Here, we make a change in this apportionment that leads to a substantial improvement in the resultant spectroscopy by including a timelike confining vector potential over and above the scalar confining one and the electromagnetic-like vector potential. Our fit includes 19 more mesons than the earlier results and we modify the scalar portion of the potential in such a way that allows this formalism to account for the isoscalar mesons η and η' not included in the previous work. Continuing the comparisons of formalisms and spectral results made in the previous paper with other approaches to meson spectroscopy, we examine in this paper the quasipotential approach of Ebert, Faustov, and Galkin.

  7. New Two-Body Regularization

    NASA Astrophysics Data System (ADS)

    Fukushima, Toshio

    2007-01-01

    We present a new scheme to regularize a three-dimensional two-body problem under perturbations. It is a combination of Sundman's time transformation and Levi-Civita's spatial coordinate transformation applied to the two-dimensional components of the position and velocity vectors in the osculating orbital plane. We adopt a coordinate triad specifying the plane as a function of the orbital angular momentum vector only. Since the magnitude of the orbital angular momentum is explicitly computed from the in-the-plane components of the position and velocity vectors, only two components of the orbital angular momentum vector are to be determined. In addition to these, we select the total energy of the two-body system and the physical time as additional components of the new variables. The equations of motion of the new variables have no singularity even when the mutual distance is extremely small, and therefore, the new variables are suitable to deal with close encounters. As a result, the number of dependent variables in the new scheme becomes eight, which is significantly smaller than the existing schemes to avoid close encounters: two less than the Kustaanheimo-Stiefel and the Bürdet-Ferrandiz regularizations, and five less than the Sperling-Bürdet/Bürdet-Heggie regularization.

  8. Features of Ar solvation shells in neutral and ionic clustering: the competitive role of two-body and many-body interactions.

    PubMed

    Albertí, Margarita; Pirani, Fernando

    2011-06-23

    The semiempirical methodology, introduced to describe noncovalent intermolecular interactions in atom/ion-molecule systems, is here extended to investigate a prototype cluster, formed by benzene (Bz) and closed-shell ions (Na(+) and/or Cl(-)), surrounded by neutral species (Ar), forming solvation shells. The involved multidimensional potential energy surface (PES) is assumed to depend on a critical balancing of some effective interaction components. In particular, for the Ar solvated Bz-Na(+)-Cl(-) system, the nonelectrostatic component of the total interaction has been formulated as a combination of two-, three-, and four-body contributions, each one represented by a proper function, with the four-body and part of the three-body terms arising from nonadditive induction effects. The proposed formulation, in which the induction is included both implicitly and explicitly, ensures the accurate description of all dissociation channels, leading to simpler clusters and/or pure solvent. Some properties of the solvent, represented by an ensemble of 500 Ar atoms, have been analyzed by performing molecular dynamics simulations at several temperatures. The obtained results have been found to be consistent with experimental observations. In order to investigate propensities, similarities, and differences in the competing clusters, the Ar solvation shells of Bz, Bz-Na(+), Bz-Cl(-) and Bz-Na(+)-Cl(-) have been characterized. The inspection of the solvation shell of Bz allows one to distinguish between groups of Ar atoms occupying positions on and out of the plane defined by the aromatic ring. Regarding the solvation shells of Bz-Na(+) and Bz-Cl(-), it has been observed that they are strongly affected by the most stable structures of the unsolvated systems. However, Bz-Na(+) shows more compact solvation shells than Bz-Cl(-). Finally, important asymmetries, basically promoted by the additional many-body induction effects on the solvent atoms, have been observed in the solvation

  9. Five ab initio potential energy and dipole moment surfaces for hydrated NaCl and NaF. I. Two-body interactions.

    PubMed

    Wang, Yimin; Bowman, Joel M; Kamarchik, Eugene

    2016-03-21

    We report full-dimensional, ab initio-based potentials and dipole moment surfaces for NaCl, NaF, Na(+)H2O, F(-)H2O, and Cl(-)H2O. The NaCl and NaF potentials are diabatic ones that dissociate to ions. These are obtained using spline fits to CCSD(T)/aug-cc-pV5Z energies. In addition, non-linear least square fits using the Born-Mayer-Huggins potential are presented, providing accurate parameters based strictly on the current ab initio energies. The long-range behavior of the NaCl and NaF potentials is shown to go, as expected, accurately to the point-charge Coulomb interaction. The three ion-H2O potentials are permutationally invariant fits to roughly 20,000 coupled cluster CCSD(T) energies (awCVTZ basis for Na(+) and aVTZ basis for Cl(-) and F(-)), over a large range of distances and H2O intramolecular configurations. These potentials are switched accurately in the long range to the analytical ion-dipole interactions, to improve computational efficiency. Dipole moment surfaces are fits to MP2 data; for the ion-ion cases, these are well described in the intermediate- and long-range by the simple point-charge expression. The performance of these new fits is examined by direct comparison to additional ab initio energies and dipole moments along various cuts. Equilibrium structures, harmonic frequencies, and electronic dissociation energies are also reported and compared to direct ab initio results. These indicate the high fidelity of the new PESs.

  10. Five ab initio potential energy and dipole moment surfaces for hydrated NaCl and NaF. I. Two-body interactions

    NASA Astrophysics Data System (ADS)

    Wang, Yimin; Bowman, Joel M.; Kamarchik, Eugene

    2016-03-01

    We report full-dimensional, ab initio-based potentials and dipole moment surfaces for NaCl, NaF, Na+H2O, F-H2O, and Cl-H2O. The NaCl and NaF potentials are diabatic ones that dissociate to ions. These are obtained using spline fits to CCSD(T)/aug-cc-pV5Z energies. In addition, non-linear least square fits using the Born-Mayer-Huggins potential are presented, providing accurate parameters based strictly on the current ab initio energies. The long-range behavior of the NaCl and NaF potentials is shown to go, as expected, accurately to the point-charge Coulomb interaction. The three ion-H2O potentials are permutationally invariant fits to roughly 20 000 coupled cluster CCSD(T) energies (awCVTZ basis for Na+ and aVTZ basis for Cl- and F-), over a large range of distances and H2O intramolecular configurations. These potentials are switched accurately in the long range to the analytical ion-dipole interactions, to improve computational efficiency. Dipole moment surfaces are fits to MP2 data; for the ion-ion cases, these are well described in the intermediate- and long-range by the simple point-charge expression. The performance of these new fits is examined by direct comparison to additional ab initio energies and dipole moments along various cuts. Equilibrium structures, harmonic frequencies, and electronic dissociation energies are also reported and compared to direct ab initio results. These indicate the high fidelity of the new PESs.

  11. Optimization of therapeutic proteins to delete T-cell epitopes while maintaining beneficial residue interactions.

    PubMed

    Parker, Andrew S; Griswold, Karl E; Bailey-Kellogg, Chris

    2011-04-01

    Exogenous enzymes, signaling peptides, and other classes of nonhuman proteins represent a potentially massive but largely untapped pool of biotherapeutic agents. Adapting a foreign protein for therapeutic use poses numerous design challenges. We focus here on one significant problem: modifying the protein to mitigate the immune response mounted against "non-self" proteins, while not adversely affecting the protein's stability or therapeutic activity. In order to propose such variants suitable for experimental evaluation, this paper develops a computational method to select sets of mutations predicted to delete immunogenic T-cell epitopes, as evaluated by a 9-mer potential, while simultaneously maintaining important residues and residue interactions, as evaluated by one- and two-body potentials. While this design problem is NP-hard, we develop an integer programming approach that works very well in practice. We demonstrate the effectiveness of our approach by developing plans for biotherapeutic proteins that, in previous studies, have been partially deimmunized via extensive experimental characterization and modification of limited segments. In contrast, our global optimization technique considers an entire protein and accounts for all residues, residue interactions, and epitopes in proposing candidates worth subjecting to experimental evaluation.

  12. Orbits of Two-Body Problem From the Lenz Vector

    ERIC Educational Resources Information Center

    Caplan, S.; And Others

    1978-01-01

    Obtains the orbits with reference to the center of mass of two bodies under mutual universe square law interaction by use of the eccentricity vector which is equivalent to the Lenz vector within a numerical factor. (Author/SL)

  13. Universal two-body-Hamiltonian quantum computing

    NASA Astrophysics Data System (ADS)

    Nagaj, Daniel

    2012-03-01

    We present a Hamiltonian quantum-computation scheme universal for quantum computation. Our Hamiltonian is a sum of a polynomial number (in the number of gates L in the quantum circuit) of constant-norm, time-independent, two-body interaction terms. Furthermore, each qubit in the system interacts only with a constant number of other qubits in a three-layer, geometrically local layout. The computer runs in three steps—it starts in a simple initial product state, evolves according to a time-independent Hamiltonian for time of order L2 (up to logarithmic factors), and finishes with a two-qubit measurement. Our model improves previous universal two-local-Hamiltonian constructions, as it avoids using perturbation gadgets and large energy-penalty terms in the Hamiltonian, which would result in a large required run time.

  14. Prediction of interface residue based on the features of residue interaction network.

    PubMed

    Jiao, Xiong; Ranganathan, Shoba

    2017-11-07

    Protein-protein interaction plays a crucial role in the cellular biological processes. Interface prediction can improve our understanding of the molecular mechanisms of the related processes and functions. In this work, we propose a classification method to recognize the interface residue based on the features of a weighted residue interaction network. The random forest algorithm is used for the prediction and 16 network parameters and the B-factor are acting as the element of the input feature vector. Compared with other similar work, the method is feasible and effective. The relative importance of these features also be analyzed to identify the key feature for the prediction. Some biological meaning of the important feature is explained. The results of this work can be used for the related work about the structure-function relationship analysis via a residue interaction network model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Enhancing interacting residue prediction with integrated contact matrix prediction in protein-protein interaction.

    PubMed

    Du, Tianchuan; Liao, Li; Wu, Cathy H

    2016-12-01

    Identifying the residues in a protein that are involved in protein-protein interaction and identifying the contact matrix for a pair of interacting proteins are two computational tasks at different levels of an in-depth analysis of protein-protein interaction. Various methods for solving these two problems have been reported in the literature. However, the interacting residue prediction and contact matrix prediction were handled by and large independently in those existing methods, though intuitively good prediction of interacting residues will help with predicting the contact matrix. In this work, we developed a novel protein interacting residue prediction system, contact matrix-interaction profile hidden Markov model (CM-ipHMM), with the integration of contact matrix prediction and the ipHMM interaction residue prediction. We propose to leverage what is learned from the contact matrix prediction and utilize the predicted contact matrix as "feedback" to enhance the interaction residue prediction. The CM-ipHMM model showed significant improvement over the previous method that uses the ipHMM for predicting interaction residues only. It indicates that the downstream contact matrix prediction could help the interaction site prediction.

  16. Direct coevolutionary couplings reflect biophysical residue interactions in proteins

    NASA Astrophysics Data System (ADS)

    Coucke, Alice; Uguzzoni, Guido; Oteri, Francesco; Cocco, Simona; Monasson, Remi; Weigt, Martin

    2016-11-01

    Coevolution of residues in contact imposes strong statistical constraints on the sequence variability between homologous proteins. Direct-Coupling Analysis (DCA), a global statistical inference method, successfully models this variability across homologous protein families to infer structural information about proteins. For each residue pair, DCA infers 21 × 21 matrices describing the coevolutionary coupling for each pair of amino acids (or gaps). To achieve the residue-residue contact prediction, these matrices are mapped onto simple scalar parameters; the full information they contain gets lost. Here, we perform a detailed spectral analysis of the coupling matrices resulting from 70 protein families, to show that they contain quantitative information about the physico-chemical properties of amino-acid interactions. Results for protein families are corroborated by the analysis of synthetic data from lattice-protein models, which emphasizes the critical effect of sampling quality and regularization on the biochemical features of the statistical coupling matrices.

  17. Direct coevolutionary couplings reflect biophysical residue interactions in proteins.

    PubMed

    Coucke, Alice; Uguzzoni, Guido; Oteri, Francesco; Cocco, Simona; Monasson, Remi; Weigt, Martin

    2016-11-07

    Coevolution of residues in contact imposes strong statistical constraints on the sequence variability between homologous proteins. Direct-Coupling Analysis (DCA), a global statistical inference method, successfully models this variability across homologous protein families to infer structural information about proteins. For each residue pair, DCA infers 21 × 21 matrices describing the coevolutionary coupling for each pair of amino acids (or gaps). To achieve the residue-residue contact prediction, these matrices are mapped onto simple scalar parameters; the full information they contain gets lost. Here, we perform a detailed spectral analysis of the coupling matrices resulting from 70 protein families, to show that they contain quantitative information about the physico-chemical properties of amino-acid interactions. Results for protein families are corroborated by the analysis of synthetic data from lattice-protein models, which emphasizes the critical effect of sampling quality and regularization on the biochemical features of the statistical coupling matrices.

  18. Bioinformatic prediction and in vivo validation of residue-residue interactions in human proteins

    NASA Astrophysics Data System (ADS)

    Jordan, Daniel; Davis, Erica; Katsanis, Nicholas; Sunyaev, Shamil

    2014-03-01

    Identifying residue-residue interactions in protein molecules is important for understanding both protein structure and function in the context of evolutionary dynamics and medical genetics. Such interactions can be difficult to predict using existing empirical or physical potentials, especially when residues are far from each other in sequence space. Using a multiple sequence alignment of 46 diverse vertebrate species we explore the space of allowed sequences for orthologous protein families. Amino acid changes that are known to damage protein function allow us to identify specific changes that are likely to have interacting partners. We fit the parameters of the continuous-time Markov process used in the alignment to conclude that these interactions are primarily pairwise, rather than higher order. Candidates for sites under pairwise epistasis are predicted, which can then be tested by experiment. We report the results of an initial round of in vivo experiments in a zebrafish model that verify the presence of multiple pairwise interactions predicted by our model. These experimentally validated interactions are novel, distant in sequence, and are not readily explained by known biochemical or biophysical features.

  19. On the relation between residue flexibility and residue interactions in proteins.

    PubMed

    Yin, Hui; Li, Yi-Zhou; Li, Meng-Long

    2011-05-01

    B-factor from X-ray crystal structure can well measure protein structural flexibility, which plays an important role in different biological processes, such as catalysis, binding and molecular recognition. Understanding the essence of flexibility can be helpful for the further study of the protein function. In this study, we attempted to correlate the flexibility of a residue to its interactions with other residues by representing the protein structure as a residue contact network. Here, several well established network topological parameters were employed to feature such interactions. A prediction model was constructed for B-factor of a residue by using support vector regression (SVR). Pearson correlation coefficient (CC) was used as the performance measure. CC values were 0.63 and 0.62 for single amino acid and for the whole sequence, respectively. Our results revealed well correlations between B-factors and network topological parameters. This suggests that the protein structural flexibility could be well characterized by the inter-amino acid interactions in a protein.

  20. Separable approximation to two-body matrix elements

    SciTech Connect

    Robledo, Luis M.

    2010-04-15

    Two-body matrix elements of arbitrary local interactions are written as the sum of separable terms in a way that is well suited for the exchange and pairing channels present in mean-field calculations. The expansion relies on the transformation to center of mass and relative coordinate (in the spirit of Talmi's method) and therefore it is only useful (finite number of expansion terms) for harmonic oscillator single particle states. The converge of the expansion with the number of terms retained is studied for a Gaussian two body interaction. The limit of a contact (delta) force is also considered. Ways to handle the general case are also discussed.

  1. Wave Function Structure in Two-Body Random Matrix Ensembles

    SciTech Connect

    Kaplan, Lev; Papenbrock, Thomas

    2000-05-15

    We study the structure of eigenstates in two-body interaction random matrix ensembles and find significant deviations from random matrix theory expectations. The deviations are most prominent in the tails of the spectral density and indicate localization of the eigenstates in Fock space. Using ideas related to scar theory we derive an analytical formula that relates fluctuations in wave function intensities to fluctuations of the two-body interaction matrix elements. Numerical results for many-body fermion systems agree well with the theoretical predictions. (c) 2000 The American Physical Society.

  2. The residual proton-neutron interaction and nuclear collectivity

    SciTech Connect

    Casten, R.F.

    1990-01-01

    The essential role of the valence, residual p-n interaction in the development of collectivity, though long known in general terms, has recently become increasingly apparent. A brief review of the p-n interaction is given, including some very basic nuclear data that illustrate its effects and the phenomenological N{sub p}N{sub n} scheme and the P-factor. This is followed by a discussion of recent experimental extractions of p-n matrix elements throughout the periodic table and theoretical efforts to understand them, in terms of both Shell and Nilsson models. 20 refs., 13 figs.

  3. Tissue factor residues that putatively interact with membrane phospholipids.

    PubMed

    Ke, Ke; Yuan, Jian; Morrissey, James H

    2014-01-01

    Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit), bound to the integral membrane protein, tissue factor (the regulatory subunit). Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue factor/factor VIIa complex relative to its membrane-bound protein substrates, factors IX and X. In this study, we individually mutated to alanine all the putative phosphatidylserine-interactive residues in the tissue factor ectodomain and measured their effects on tissue factor cofactor function (activation of factors IX and X by tissue factor/factor VIIa, and clotting of plasma). Some tissue factor mutants exhibited decreased activity in all three assays, with the most profound defects observed from mutations in or near the flexible loop from Lys159 to Gly164. The decreased activity of all of these tissue factor mutants could be partially or completely overcome by increasing the phosphatidylserine content of tissue factor-liposomes. Additionally, yeast surface display was used to screen a random library of tissue factor mutants for enhanced factor VIIa binding. Surprisingly, mutations at a single amino acid (Lys165) predominated, with the Lys165→Glu mutant exhibiting a 3-fold enhancement in factor VIIa binding affinity. Our studies reveal the functional contributions of residues in the C-terminal half of the tissue factor ectodomain that are implicated in interacting with phosphatidylserine headgroups to enhance tissue factor cofactor activity, possibly by allosterically modulating the conformation of the adjacent substrate-binding exosite region of tissue factor.

  4. Controller-structure interaction compensation using adaptive residual mode filters

    NASA Technical Reports Server (NTRS)

    Davidson, Roger A.; Balas, Mark J.

    1990-01-01

    It is not feasible to construct controllers for large space structures or large scale systems (LSS's) which are of the same order as the structures. The complexity of the dynamics of these systems is such that full knowledge of its behavior cannot by processed by today's controller design methods. The controller for system performance of such a system is therefore based on a much smaller reduced-order model (ROM). Unfortunately, the interaction between the LSS and the ROM-based controller can produce instabilities in the closed-loop system due to the unmodeled dynamics of the LSS. Residual mode filters (RMF's) allow the systematic removal of these instabilities in a matter which does not require a redesign of the controller. In addition RMF's have a strong theoretical basis. As simple first- or second-order filters, the RMF CSI compensation technique is at once modular, simple and highly effective. RMF compensation requires knowledge of the dynamics of the system modes which resulted in the previous closed-loop instabilities (the residual modes), but this information is sometimes known imperfectly. An adaptive, self-tuning RMF design, which compensates for uncertainty in the frequency of the residual mode, has been simulated using continuous-time and discrete-time models of a flexible robot manipulator. Work has also been completed on the discrete-time experimental implementation on the Martin Marietta flexible robot manipulator experiment. This paper will present the results of that work on adaptive, self-tuning RMF's, and will clearly show the advantage of this adaptive compensation technique for controller-structure interaction (CSI) instabilities in actively-controlled LSS's.

  5. Interpreting Interactions between Ozone and Residual Petroleum Hydrocarbons in Soil.

    PubMed

    Chen, Tengfei; Delgado, Anca G; Yavuz, Burcu M; Maldonado, Juan; Zuo, Yi; Kamath, Roopa; Westerhoff, Paul; Krajmalnik-Brown, Rosa; Rittmann, Bruce E

    2017-01-03

    We evaluated how gas-phase O3 interacts with residual petroleum hydrocarbons in soil. Total petroleum hydrocarbons (TPH) were 18 ± 0.6 g/kg soil, and TPH carbon constituted ∼40% of the dichloromethane-extractable carbon (DeOC) in the soil. At the benchmark dose of 3.4 kg O3/kg initial TPH, TPH carbon was reduced by nearly 6 gC/kg soil (40%), which was accompanied by an increase of about 4 gC/kg soil in dissolved organic carbon (DOC) and a 4-fold increase in 5-day biochemical oxygen demand (BOD5). Disrupting gas channeling in the soil improved mass transport of O3 to TPH bound to soil and increased TPH removal. Ozonation resulted in two measurable alterations of the composition of the organic carbon. First, part of DeOC was converted to DOC (∼4.1 gC/kg soil), 75% of which was not extractable by dichloromethane. Second, the DeOC containing saturates, aromatics, resins, and asphaltenes (SARA), was partially oxidized, resulting in a decline in saturates and aromatics, but increases in resins and asphaltenes. Ozone attack on resins, asphaltenes, and soil organic matter led to the production of NO3(-), SO4(2-), and PO4(3-). The results illuminate the mechanisms by which ozone gas interacted with the weathered petroleum residuals in soil to generate soluble and biodegradable products.

  6. Pinpointing Biphenyl Dioxygenase Residues That Are Crucial for Substrate Interaction

    PubMed Central

    Zielinski, Marco; Kahl, Silke; Hecht, Hans-Jürgen; Hofer, Bernd

    2003-01-01

    Three regions of the biphenyl dioxygenase (BDO) of Burkholderia sp. strain LB400 have previously been shown to significantly influence the interaction between enzyme and substrates at the active site. For a further discrimination within these regions, we investigated the effects of 23 individual amino acid exchanges. The regiospecificity of substrate dioxygenation was used as a sensitive means to monitor changes in the steric-electronic structure of the active site. Replacements of residues that, according to a model of the BDO three-dimensional structure, directly interact with substrates in most, but not all, cases (Met231, Phe378, and Phe384) very strongly altered this parameter (by factors of >7). On the other hand, a number of amino acids (Ile243, Ile326, Phe332, Pro334, and Trp392) which have no contacts with substrates also strongly changed the site preference of dioxygenation (by factors of between 2.6 and 3.5). This demonstrates that residues which had not been predicted to be influential can play a pivotal role in BDO specificity. PMID:14617661

  7. Structured residual technique for malfunction isolation in interacting systems

    SciTech Connect

    Hardy, C.R.; Miller, D.W.; Hajek, B.K. )

    1992-01-01

    Researchers in the field of fault detection and isolation have presented schemes for diagnosing faults in systems in the presence of unknown input disturbances. These techniques, known collectively as input disturbance decoupling, can be used to isolate a particular system from other systems in a complex process plant. The ability to isolate the operation of a system from systems with which it interacts is desirable when diagnosing faults in complex plants. The diagnosis problem can then be broken down into a set of relatively simple diagnostic tasks and the results evaluated using a knowledge-based approach. One such approach, known as hierarchical classification, has been used for malfunction diagnosis in both nuclear power and chemical plants. Systems that strongly interact are common in nuclear power plants. For example, in the simplified boiling water reactor (BWR) pressure control system (PCS) model of Fig. 1, steam flow from the main steam lines collects in the steam header. The header acts as a source of steam to several plant systems besides the high-pressure turbine. Thus, a change in any one of these auxiliary systems will affect the operation of the PCS. These unmeasured influences complicate the problem of isolating the PCS from the remainder of the plant. The authors have used structured residuals as a disturbance decoupling technique to isolate interacting systems in a BWR model. In this paper, we provide a brief summary of the method and show an example of its application.

  8. Prediction of residue-residue contact matrix for protein-protein interaction with Fisher score features and deep learning.

    PubMed

    Du, Tianchuan; Liao, Li; Wu, Cathy H; Sun, Bilin

    2016-11-01

    Protein-protein interactions play essential roles in many biological processes. Acquiring knowledge of the residue-residue contact information of two interacting proteins is not only helpful in annotating functions for proteins, but also critical for structure-based drug design. The prediction of the protein residue-residue contact matrix of the interfacial regions is challenging. In this work, we introduced deep learning techniques (specifically, stacked autoencoders) to build deep neural network models to tackled the residue-residue contact prediction problem. In tandem with interaction profile Hidden Markov Models, which was used first to extract Fisher score features from protein sequences, stacked autoencoders were deployed to extract and learn hidden abstract features. The deep learning model showed significant improvement over the traditional machine learning model, Support Vector Machines (SVM), with the overall accuracy increased by 15% from 65.40% to 80.82%. We showed that the stacked autoencoders could extract novel features, which can be utilized by deep neural networks and other classifiers to enhance learning, out of the Fisher score features. It is further shown that deep neural networks have significant advantages over SVM in making use of the newly extracted features.

  9. Separable approximation method for two-body relativistic scattering

    NASA Astrophysics Data System (ADS)

    Tandy, P. C.; Thaler, R. M.

    1988-03-01

    A method for defining a separable approximation to a given interaction within a two-body relativistic equation, such as the Bethe-Salpeter equation, is presented. The rank-N separable representation given here permits exact reproduction of the T matrix on the mass shell and half off the mass shell at N selected bound state and/or continuum values of the invariant mass. The method employed is a four-space generalization of the separable representation developed for Schrödinger interactions by Ernst, Shakin, and Thaler, supplemented by procedures for dealing with the relativistic spin structure in the case of Dirac particles.

  10. Two-body scattering without angular-momentum decomposition

    SciTech Connect

    Rodriguez-Gallardo, M.; Deltuva, A.; Cravo, E.; Fonseca, A. C.; Crespo, R.

    2008-09-15

    Two-body scattering is studied by solving the Lippmann-Schwinger equation in momentum space without angular-momentum decomposition for a local spin-dependent short-range interaction plus Coulomb. The screening and renormalization approach is employed to treat the Coulomb interaction. Benchmark calculations are performed by comparing our procedure with partial-wave calculations in configuration space for p-{sup 10}Be,p-{sup 16}O, and {sup 12}C-{sup 10}Be elastic scattering, using a simple optical potential model.

  11. Numerical Comparison of Two-Body Regularizations

    NASA Astrophysics Data System (ADS)

    Fukushima, Toshio

    2007-06-01

    We numerically compare four schemes to regularize a three-dimensional two-body problem under perturbations: the Sperling-Bürdet (S-B), Kustaanheimo-Stiefel (K-S), and Bürdet-Ferrandiz (B-F) regularizations, and a three-dimensional extension of the Levi-Civita (L-C) regularization we developed recently. As for the integration time of the equation of motion, the least time is needed for the unregularized treatment, followed by the K-S, the extended L-C, the B-F, and the S-B regularizations. However, these differences become significantly smaller when the time to evaluate perturbations becomes dominant. As for the integration error after one close encounter, the K-S and the extended L-C regularizations are tied for the least error, followed by the S-B, the B-F, and finally the unregularized scheme for unperturbed orbits with eccentricity less than 2. This order is not changed significantly by various kinds of perturbations. As for the integration error of elliptical orbits after multiple orbital periods, the situation remains the same except for the rank of the S-B scheme, which varies from the best to the second worst depending on the length of integration and/or on the nature of perturbations. Also, we confirm that Kepler energy scaling enhances the performance of the unregularized, K-S, and extended L-C schemes. As a result, the K-S and the extended L-C regularizations with Kepler energy scaling provide the best cost performance in integrating almost all the perturbed two-body problems.

  12. Two-body bound states & the Bethe-Salpeter equation

    SciTech Connect

    Pichowsky, M.; Kennedy, M.; Strickland, M.

    1995-01-18

    The Bethe-Salpeter formalism is used to study two-body bound states within a scalar theory: two scalar fields interacting via the exchange of a third massless scalar field. The Schwinger-Dyson equation is derived using functional and diagrammatic techniques, and the Bethe-Salpeter equation is obtained in an analogous way, showing it to be a two-particle generalization of the Schwinger-Dyson equation. The authors also present a numerical method for solving the Bethe-Salpeter equation without three-dimensional reduction. The ground and first excited state masses and wavefunctions are computed within the ladder approximation and space-like form factors are calculated.

  13. Covariant Hamiltonian for the electromagnetic two-body problem

    NASA Astrophysics Data System (ADS)

    De Luca, Jayme

    2005-09-01

    We give a Hamiltonian formalism for the delay equations of motion of the electromagnetic two-body problem with arbitrary masses and with either repulsive or attractive interaction. This dynamical system based on action-at-a-distance electrodynamics appeared 100 years ago and it was popularized in the 1940s by the Wheeler and Feynman program to quantize it as a means to overcome the divergencies of perturbative QED. Our finite-dimensional implicit Hamiltonian is closed and involves no series expansions. As an application, the Hamiltonian formalism is used to construct a semiclassical canonical quantization based on the numerical trajectories of the attractive problem.

  14. Covariant Hamiltonian for the electromagnetic two-body problem.

    PubMed

    De Luca, Jayme

    2005-09-01

    We give a Hamiltonian formalism for the delay equations of motion of the electromagnetic two-body problem with arbitrary masses and with either repulsive or attractive interaction. This dynamical system based on action-at-a-distance electrodynamics appeared 100 years ago and it was popularized in the 1940s by the Wheeler and Feynman program to quantize it as a means to overcome the divergencies of perturbative QED. Our finite-dimensional implicit Hamiltonian is closed and involves no series expansions. As an application, the Hamiltonian formalism is used to construct a semiclassical canonical quantization based on the numerical trajectories of the attractive problem.

  15. Degeneracies when T=0 two body interaction matrix elements are set equal to zero: Talmi's method of calculating coefficients of fractional parentage to states forbidden by the Pauli principle

    NASA Astrophysics Data System (ADS)

    Robinson, Shadow J. Q.; Zamick, Larry

    2001-11-01

    In a previous work [S.J.Q. Robinson and Larry Zamick, Phys. Rev. C 63, 064416 (2001)] we studied the effects of setting all two body T=0 matrix elements to zero in shell model calculations for 43Ti (43Sc) and 44Ti. The results for 44Ti were surprisingly good despite the severity of this approximation. In single-j shell calculations (fn7/2) degeneracies arose between the T=12 I=(12)-1 and (132)-1 states in 43Sc as well as the T=12 I=(132)-2, (172)-1, and (192)-1 in 43Sc. For 44Ti the T=0 states 3+2, 7+2, 9+1, and 10+1 are degenerate as are the 10+2 and 12+1 states. The degeneracies can be explained by certain 6j symbols and 9j symbols either vanishing or being equal as indeed they are. Previously we used Regge symmetries of 6j symbols to explain the vanishing 6j and 9j symbols. In this work a simpler, more physical method is used. This is Talmi's method of calculating coefficients of fractional parentage (cfp) for identical particles to states which are forbidden by the Pauli principle. This is done for both the one particle cfp to handle 6j symbols and the two particle cfp for the 9j symbols. From this we learn that the common thread for the angular momenta I for which the above degeneracies occur is that these angular momenta cannot exist in the calcium isotopes in the f7/2 shell. There are no T=32 f37/2 states with angular momenta 12, 132, 172, and 192. In the same vein there are no T=2 f47/2 states with angular momenta 3, 7, 9, 10, or 12. For these angular momenta, all the states can be classified by the dual quantum numbers (Jπ,Jν).

  16. A critical analysis of computational protein design with sparse residue interaction graphs.

    PubMed

    Jain, Swati; Jou, Jonathan D; Georgiev, Ivelin S; Donald, Bruce R

    2017-03-01

    Protein design algorithms enumerate a combinatorial number of candidate structures to compute the Global Minimum Energy Conformation (GMEC). To efficiently find the GMEC, protein design algorithms must methodically reduce the conformational search space. By applying distance and energy cutoffs, the protein system to be designed can thus be represented using a sparse residue interaction graph, where the number of interacting residue pairs is less than all pairs of mutable residues, and the corresponding GMEC is called the sparse GMEC. However, ignoring some pairwise residue interactions can lead to a change in the energy, conformation, or sequence of the sparse GMEC vs. the original or the full GMEC. Despite the widespread use of sparse residue interaction graphs in protein design, the above mentioned effects of their use have not been previously analyzed. To analyze the costs and benefits of designing with sparse residue interaction graphs, we computed the GMECs for 136 different protein design problems both with and without distance and energy cutoffs, and compared their energies, conformations, and sequences. Our analysis shows that the differences between the GMECs depend critically on whether or not the design includes core, boundary, or surface residues. Moreover, neglecting long-range interactions can alter local interactions and introduce large sequence differences, both of which can result in significant structural and functional changes. Designs on proteins with experimentally measured thermostability show it is beneficial to compute both the full and the sparse GMEC accurately and efficiently. To this end, we show that a provable, ensemble-based algorithm can efficiently compute both GMECs by enumerating a small number of conformations, usually fewer than 1000. This provides a novel way to combine sparse residue interaction graphs with provable, ensemble-based algorithms to reap the benefits of sparse residue interaction graphs while avoiding their

  17. A critical analysis of computational protein design with sparse residue interaction graphs

    PubMed Central

    Georgiev, Ivelin S.

    2017-01-01

    Protein design algorithms enumerate a combinatorial number of candidate structures to compute the Global Minimum Energy Conformation (GMEC). To efficiently find the GMEC, protein design algorithms must methodically reduce the conformational search space. By applying distance and energy cutoffs, the protein system to be designed can thus be represented using a sparse residue interaction graph, where the number of interacting residue pairs is less than all pairs of mutable residues, and the corresponding GMEC is called the sparse GMEC. However, ignoring some pairwise residue interactions can lead to a change in the energy, conformation, or sequence of the sparse GMEC vs. the original or the full GMEC. Despite the widespread use of sparse residue interaction graphs in protein design, the above mentioned effects of their use have not been previously analyzed. To analyze the costs and benefits of designing with sparse residue interaction graphs, we computed the GMECs for 136 different protein design problems both with and without distance and energy cutoffs, and compared their energies, conformations, and sequences. Our analysis shows that the differences between the GMECs depend critically on whether or not the design includes core, boundary, or surface residues. Moreover, neglecting long-range interactions can alter local interactions and introduce large sequence differences, both of which can result in significant structural and functional changes. Designs on proteins with experimentally measured thermostability show it is beneficial to compute both the full and the sparse GMEC accurately and efficiently. To this end, we show that a provable, ensemble-based algorithm can efficiently compute both GMECs by enumerating a small number of conformations, usually fewer than 1000. This provides a novel way to combine sparse residue interaction graphs with provable, ensemble-based algorithms to reap the benefits of sparse residue interaction graphs while avoiding their

  18. Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor.

    PubMed Central

    Zurawski, S M; Vega, F; Doyle, E L; Huyghe, B; Flaherty, K; McKay, D B; Zurawski, G

    1993-01-01

    The high affinity receptor for interleukin-2 (IL-2) contains three subunits called IL-2R alpha, beta and gamma. A biological and receptor binding analysis based on 1393 different mutant mouse IL-2 (mIL-2) proteins was used to define the function of each of the 149 residues. By this genetic analysis, 44 residues were assigned important functions, 21 of which were structural. The remaining 23 residues consisted of 19 residues, from three separate regions, that were important for IL-2R alpha interaction; three residues, from two separate regions, that were important for IL-2R beta interaction; and a single residue important for IL-2R gamma interaction. We built a model mIL-2 structure based on the homologous human IL-2 (hIL-2) crystal structure. The roles of the 21 residues presumed to be important for structure were consistent with the model. Despite discontinuity in the primary sequence, the residues specific for each IL-2R subunit interaction were clustered and located to three disparate regions of the tertiary mIL-2 structure. The relative spatial locations of these three surfaces are different from the two receptor binding sites known for the structurally related human growth hormone and the significance of this observation is discussed. Images PMID:8262055

  19. Prediction of vitamin interacting residues in a vitamin binding protein using evolutionary information.

    PubMed

    Panwar, Bharat; Gupta, Sudheer; Raghava, Gajendra P S

    2013-02-07

    The vitamins are important cofactors in various enzymatic-reactions. In past, many inhibitors have been designed against vitamin binding pockets in order to inhibit vitamin-protein interactions. Thus, it is important to identify vitamin interacting residues in a protein. It is possible to detect vitamin-binding pockets on a protein, if its tertiary structure is known. Unfortunately tertiary structures of limited proteins are available. Therefore, it is important to develop in-silico models for predicting vitamin interacting residues in protein from its primary structure. In this study, first we compared protein-interacting residues of vitamins with other ligands using Two Sample Logo (TSL). It was observed that ATP, GTP, NAD, FAD and mannose preferred {G,R,K,S,H}, {G,K,T,S,D,N}, {T,G,Y}, {G,Y,W} and {Y,D,W,N,E} residues respectively, whereas vitamins preferred {Y,F,S,W,T,G,H} residues for the interaction with proteins. Furthermore, compositional information of preferred and non-preferred residues along with patterns-specificity was also observed within different vitamin-classes. Vitamins A, B and B6 preferred {F,I,W,Y,L,V}, {S,Y,G,T,H,W,N,E} and {S,T,G,H,Y,N} interacting residues respectively. It suggested that protein-binding patterns of vitamins are different from other ligands, and motivated us to develop separate predictor for vitamins and their sub-classes. The four different prediction modules, (i) vitamin interacting residues (VIRs), (ii) vitamin-A interacting residues (VAIRs), (iii) vitamin-B interacting residues (VBIRs) and (iv) pyridoxal-5-phosphate (vitamin B6) interacting residues (PLPIRs) have been developed. We applied various classifiers of SVM, BayesNet, NaiveBayes, ComplementNaiveBayes, NaiveBayesMultinomial, RandomForest and IBk etc., as machine learning techniques, using binary and Position-Specific Scoring Matrix (PSSM) features of protein sequences. Finally, we selected best performing SVM modules and obtained highest MCC of 0.53, 0.48, 0.61, 0

  20. Description and evaluation of nuclear masses based on residual proton-neutron interactions

    SciTech Connect

    Fu, G. J.; Lei, Y.; Jiang, H.; Zhao, Y. M.; Sun, B.; Arima, A.

    2011-09-15

    In this paper we study the residual proton-neutron interactions and make use of the systematics of these interactions to describe experimental data of nuclear masses and to predict some of the unknown masses. The odd-even effect staggering of the residual proton-neutron interaction between the last proton and the last neutron is found and argued in terms of pairing interactions. Two local mass relations, which work very accurately for masses of four neighboring nuclei, are discovered. The accuracy of our predicted masses for medium and heavy nuclei is competitive with that of the AME2003 extrapolations, with the virtue of simplicity.

  1. The Two-Body Inversion Effect.

    PubMed

    Papeo, Liuba; Stein, Timo; Soto-Faraco, Salvador

    2017-03-01

    How does one perceive groups of people? It is known that functionally interacting objects (e.g., a glass and a pitcher tilted as if pouring water into it) are perceptually grouped. Here, we showed that processing of multiple human bodies is also influenced by their relative positioning. In a series of categorization experiments, bodies facing each other (seemingly interacting) were recognized more accurately than bodies facing away from each other (noninteracting). Moreover, recognition of facing body dyads (but not nonfacing body dyads) was strongly impaired when those stimuli were inverted, similar to what has been found for individual bodies. This inversion effect demonstrates sensitivity of the visual system to facing body dyads in their common upright configuration and might imply recruitment of configural processing (i.e., processing of the overall body configuration without prior part-by-part analysis). These findings suggest that facing dyads are represented as one structured unit, which may be the intermediate level of representation between multiple-object (body) perception and representation of social actions.

  2. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    PubMed

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations.

  3. Unconstrained Structural Equation Models of Latent Interactions: Contrasting Residual- and Mean-Centered Approaches

    ERIC Educational Resources Information Center

    Marsh, Herbert W.; Wen, Zhonglin; Hau, Kit-Tai; Little, Todd D.; Bovaird, James A.; Widaman, Keith F.

    2007-01-01

    Little, Bovaird and Widaman (2006) proposed an unconstrained approach with residual centering for estimating latent interaction effects as an alternative to the mean-centered approach proposed by Marsh, Wen, and Hau (2004, 2006). Little et al. also differed from Marsh et al. in the number of indicators used to infer the latent interaction factor…

  4. Ionization States of Residues in OmpF and Mutants: Effects of Dielectric Constant and Interactions between Residues

    PubMed Central

    Varma, Sameer; Jakobsson, Eric

    2004-01-01

    To understand ion permeation, one must assign correct ionization states to titratable amino acid residues in protein channels. We report on the effects of physical and methodological assumptions in calculating the protonation states at neutral bulk pH of titratable residues lining the lumen of the native Escherichia coli OmpF channel, and five mutants. We systematically considered a wide range of assumed protein dielectric constants and all plausible combinations of protonation states for electrostatically interacting side chains, and three different levels of accounting for solute shielding: 1), full nonlinear Poisson-Boltzmann; 2), linearized Poisson-Boltzmann; and 3), neglect of solute shielding. For this system we found it acceptable to neglect solute shielding, a result we postulate to be generalizable to narrow lumens of other protein channels. For the large majority of residues, the protonation state at neutral bulk pH was found to be independent of the assumed dielectric constant of the protein, and unambiguously determined by the calculation; for native OmpF only Asp-127 has a protonation state that is sensitive to the assumed protein dielectric constant. Our results are significant for understanding two published experimental observations: the structure of the narrow part of the channel, and the ionic selectivity of OmpF mutants. PMID:14747308

  5. Ionization states of residues in OmpF and mutants: effects of dielectric constant and interactions between residues.

    PubMed

    Varma, Sameer; Jakobsson, Eric

    2004-02-01

    To understand ion permeation, one must assign correct ionization states to titratable amino acid residues in protein channels. We report on the effects of physical and methodological assumptions in calculating the protonation states at neutral bulk pH of titratable residues lining the lumen of the native Escherichia coli OmpF channel, and five mutants. We systematically considered a wide range of assumed protein dielectric constants and all plausible combinations of protonation states for electrostatically interacting side chains, and three different levels of accounting for solute shielding: 1), full nonlinear Poisson-Boltzmann; 2), linearized Poisson-Boltzmann; and 3), neglect of solute shielding. For this system we found it acceptable to neglect solute shielding, a result we postulate to be generalizable to narrow lumens of other protein channels. For the large majority of residues, the protonation state at neutral bulk pH was found to be independent of the assumed dielectric constant of the protein, and unambiguously determined by the calculation; for native OmpF only Asp-127 has a protonation state that is sensitive to the assumed protein dielectric constant. Our results are significant for understanding two published experimental observations: the structure of the narrow part of the channel, and the ionic selectivity of OmpF mutants.

  6. Molecular Dynamics of a Protein Surface: Ion-Residues Interactions

    PubMed Central

    Friedman, Ran; Nachliel, Esther; Gutman, Menachem

    2005-01-01

    Time-resolved measurements indicated that protons could propagate on the surface of a protein or a membrane by a special mechanism that enhanced the shuttle of the proton toward a specific site. It was proposed that a suitable location of residues on the surface contributes to the proton shuttling function. In this study, this notion was further investigated by the use of molecular dynamics simulations, where Na+ and Cl− are the ions under study, thus avoiding the necessity for quantum mechanical calculations. Molecular dynamics simulations were carried out using as a model a few Na+ and Cl− ions enclosed in a fully hydrated simulation box with a small globular protein (the S6 of the bacterial ribosome). Three independent 10-ns-long simulations indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. However, it was noted that close to some domains the ions extended their duration near the surface, thus suggesting that the local electrostatic potential hindered their diffusion to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of the molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed. PMID:15894639

  7. Protein-protein interaction interface residue pair prediction based on deep learning architecture.

    PubMed

    Zhao, Zhenni; Gong, Xinqi

    2017-05-19

    Proteins usually fulfill their biological functions by interacting with other proteins. Although some methods have been developed to predict the binding sites of a monomer protein, these are not sufficient for prediction of the interaction between two monomer proteins. The correct prediction of interface residue pairs from two monomer proteins is still an open question and has great significance for practical experimental applications in the life sciences. We hope to build a method for the prediction of interface residue pairs that is suitable for those applications. Here, we developed a novel deep network architecture called the multi-layered Long-Short Term Memory networks (LSTMs) approach for the prediction of protein interface residue pairs. Firstly, we created three new descriptions and used other six worked characterizations to describe an amino acid, then we employed these features to discriminate between interface residue pairs and non-interface residue pairs. Secondly, we used two thresholds to select residue pairs that are more likely to be interface residue pairs. Furthermore, this step increases the proportion of interface residue pairs and reduces the influence of imbalanced data. Thirdly, we built deep network architectures based on Long-Short Term Memory networks algorithm to organize and refine the prediction of interface residue pairs by employing features mentioned above. We trained the deep networks on dimers in the unbound state in the international Protein-protein Docking Benchmark version 3.0. The updated data sets in the versions 4.0 and 5.0 were used as the validation set and test set respectively. For our best model, the accuracy rate was over 62% when we chose the top 0.2% pairs of every dimer in the test set as predictions, which will be very helpful for the understanding of protein-protein interaction mechanisms and for guidance in biological experiments.

  8. Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction.

    PubMed

    Gu, Xiaodong; Huang, Ying; Levison, Bruce S; Gerstenecker, Gary; DiDonato, Anthony J; Hazen, Leah B; Lee, Joonsue; Gogonea, Valentin; DiDonato, Joseph A; Hazen, Stanley L

    2016-01-22

    Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815-3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes

  9. Identification of Critical Paraoxonase 1 Residues Involved in High Density Lipoprotein Interaction*

    PubMed Central

    Gu, Xiaodong; Huang, Ying; Levison, Bruce S.; Gerstenecker, Gary; DiDonato, Anthony J.; Hazen, Leah B.; Lee, Joonsue; Gogonea, Valentin; DiDonato, Joseph A.; Hazen, Stanley L.

    2016-01-01

    Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated protein with atherosclerosis-protective and systemic anti-oxidant functions. We recently showed that PON1, myeloperoxidase, and HDL bind to one another in vivo forming a functional ternary complex (Huang, Y., Wu, Z., Riwanto, M., Gao, S., Levison, B. S., Gu, X., Fu, X., Wagner, M. A., Besler, C., Gerstenecker, G., Zhang, R., Li, X. M., Didonato, A. J., Gogonea, V., Tang, W. H., et al. (2013) J. Clin. Invest. 123, 3815–3828). However, specific residues on PON1 involved in the HDL-PON1 interaction remain unclear. Unambiguous identification of protein residues involved in docking interactions to lipid surfaces poses considerable methodological challenges. Here we describe a new strategy that uses a novel synthetic photoactivatable and click chemistry-taggable phospholipid probe, which, when incorporated into HDL, was used to identify amino acid residues on PON1 that directly interact with the lipoprotein phospholipid surface. Several specific PON1 residues (Leu-9, Tyr-185, and Tyr-293) were identified through covalent cross-links with the lipid probes using affinity isolation coupled to liquid chromatography with on-line tandem mass spectrometry. Based upon the crystal structure for PON1, the identified residues are all localized in relatively close proximity on the surface of PON1, defining a domain that binds to the HDL lipid surface. Site-specific mutagenesis of the identified PON1 residues (Leu-9, Tyr-185, and Tyr-293), coupled with functional studies, reveals their importance in PON1 binding to HDL and both PON1 catalytic activity and stability. Specifically, the residues identified on PON1 provide important structural insights into the PON1-HDL interaction. More generally, the new photoactivatable and affinity-tagged lipid probe developed herein should prove to be a valuable tool for identifying contact sites supporting protein interactions with lipid interfaces such as found on cell membranes

  10. Ultralow field magnetization reversal of two-body magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Li, Fei; Lu, Jincheng; Lu, Xiaofeng; Tang, Rujun; Sun, Z. Z.

    2016-08-01

    Field induced magnetization reversal was investigated in a system of two magnetic nanoparticles with uniaxial anisotropies and magnetostatic interaction. By using the micromagnetic simulation, ultralow switching field strength was found when the separation distance between the two particles reaches a critical small value (on nanometer scale) in the perpendicular configuration where the anisotropic axes of the two particles are perpendicular to the separation line. The switching field increases sharply when the separation is away from the critical distance. The ultralow field switching phenomenon was missed in the parallel configuration where both the anisotropic axes are aligned along the separation line of the two particles. The micromagnetic results are consistent with the previous theoretical prediction [J. Appl. Phys. 109, 104303 (2011)] where dipolar interaction between two single-domain magnetic particles was considered. Our present simulations offered further proofs and possibilities for the low-power applications of information storage as the two-body magnetic nanoparticles might be implemented as a composite information bit.

  11. Solar System dynamics, beyond the two-body-problem approach

    NASA Astrophysics Data System (ADS)

    Varvoglis, Harry

    2006-08-01

    When one thinks of the solar system, he has usually in mind the picture based on the solution of the two-body problem approximation presented by Newton, namely the ordered clockwork motion of planets on fixed, non-intersecting orbits around the Sun. However, already by the end of the 18th century this picture was proven to be wrong. As discussed by Laplace and Lagrange (for a modern approach see [3] or [2]), the interaction between the various planets leads to secular changes in their orbits, which nevertheless were believed to be corrections of higher order to the Keplerian elliptical motion. This idea has changed completely the last decades. Now it is well know that the solar system was created from a state of chaotic interactions of planetesimals, primordial bodies the size of a small asteroid, and that since this time many episodes of cataclysmic collisions have shaken all major planets, due to the pronounced chaotic motion of the minor bodies. A new discipline has emerged out of the above new ideas, which is based on the statistical approach to chaotic motion of bodies, in particular those in the asteroid belt. At the same time it has been understood that non-gravitational forces, in particular the Yarkovsky effect, may play an important role on the long-time evolution of the trajectories of kilometer-sized bodies.

  12. Residual Symmetries and Interaction Solutions for the Classical Korteweg-de Vries Equation

    NASA Astrophysics Data System (ADS)

    Fei, Jin-Xi; Cao, Wei-Ping; Ma, Zheng-Yi

    2017-03-01

    The non-local residual symmetry for the classical Korteweg-de Vries equation is derived by the truncated Painlevé analysis. This symmetry is first localised to the Lie point symmetry by introducing the auxiliary dependent variables. By using Lie's first theorem, we then obtain the finite transformation for the localised residual symmetry. Based on the consistent tanh expansion method, some exact interaction solutions among different non-linear excitations are explicitly presented finally. Some special interaction solutions are investigated both in analytical and graphical ways at the same time.

  13. Canine Distemper Virus Envelope Protein Interactions Modulated by Hydrophobic Residues in the Fusion Protein Globular Head

    PubMed Central

    Avila, Mislay; Khosravi, Mojtaba; Alves, Lisa; Ader-Ebert, Nadine; Bringolf, Fanny; Zurbriggen, Andreas; Plemper, Richard K.

    2014-01-01

    Membrane fusion for morbillivirus cell entry relies on critical interactions between the viral fusion (F) and attachment (H) envelope glycoproteins. Through extensive mutagenesis of an F cavity recently proposed to contribute to F's interaction with the H protein, we identified two neighboring hydrophobic residues responsible for severe F-to-H binding and fusion-triggering deficiencies when they were mutated in combination. Since both residues reside on one side of the F cavity, the data suggest that H binds the F globular head domain sideways. PMID:25355896

  14. Specificity in transmembrane helix-helix interactions mediated by aromatic residues.

    PubMed

    Sal-Man, Neta; Gerber, Doron; Bloch, Itai; Shai, Yechiel

    2007-07-06

    Aromatic residues have been previously shown to mediate the self-assembly of different soluble proteins through pi-pi interactions (McGaughey, G. B., Gagne, M., and Rappe, A. K. (1998) J. Biol. Chem. 273, 15458-15463). However, their role in transmembrane (TM) assembly is not yet clear. In this study, we performed statistical analysis of the frequency of occurrence of aromatic pairs in a bacterial TM data base that provided an initial indication that the appearance of a specific aromatic pattern, Aromatic-XX-Aromatic, is not coincidental, similar to the well characterized QXXS motif. The QXXS motif was previously shown to be both critical and sufficient for stabilizing TM self-assembly. Using the ToxR system, we monitored the dimerization propensities of TM domains that contain mutations of interacting residues to aromatic amino acids and demonstrated that aromatic residues can adequately stabilize self-association. Importantly, we have provided an example of a natural TM domain, the cholera toxin secretion protein EpsM, whose TM self-assembly is mediated by an aromatic motif (WXXW). This is, in fact, the first evidence that aromatic residues are involved in the dimerization of a wild type TM domain. The association mediated by aromatic residues was found to be sensitive to the TM sequence, suggesting that aromatic residue motifs can provide a general means for specificity in TM assembly. Molecular dynamics provided a structural explanation for this backbone sequence sensitivity.

  15. Prediction of vitamin interacting residues in a vitamin binding protein using evolutionary information

    PubMed Central

    2013-01-01

    Background The vitamins are important cofactors in various enzymatic-reactions. In past, many inhibitors have been designed against vitamin binding pockets in order to inhibit vitamin-protein interactions. Thus, it is important to identify vitamin interacting residues in a protein. It is possible to detect vitamin-binding pockets on a protein, if its tertiary structure is known. Unfortunately tertiary structures of limited proteins are available. Therefore, it is important to develop in-silico models for predicting vitamin interacting residues in protein from its primary structure. Results In this study, first we compared protein-interacting residues of vitamins with other ligands using Two Sample Logo (TSL). It was observed that ATP, GTP, NAD, FAD and mannose preferred {G,R,K,S,H}, {G,K,T,S,D,N}, {T,G,Y}, {G,Y,W} and {Y,D,W,N,E} residues respectively, whereas vitamins preferred {Y,F,S,W,T,G,H} residues for the interaction with proteins. Furthermore, compositional information of preferred and non-preferred residues along with patterns-specificity was also observed within different vitamin-classes. Vitamins A, B and B6 preferred {F,I,W,Y,L,V}, {S,Y,G,T,H,W,N,E} and {S,T,G,H,Y,N} interacting residues respectively. It suggested that protein-binding patterns of vitamins are different from other ligands, and motivated us to develop separate predictor for vitamins and their sub-classes. The four different prediction modules, (i) vitamin interacting residues (VIRs), (ii) vitamin-A interacting residues (VAIRs), (iii) vitamin-B interacting residues (VBIRs) and (iv) pyridoxal-5-phosphate (vitamin B6) interacting residues (PLPIRs) have been developed. We applied various classifiers of SVM, BayesNet, NaiveBayes, ComplementNaiveBayes, NaiveBayesMultinomial, RandomForest and IBk etc., as machine learning techniques, using binary and Position-Specific Scoring Matrix (PSSM) features of protein sequences. Finally, we selected best performing SVM modules and obtained highest MCC of

  16. The Sharma-Parthasarathy stochastic two-body problem

    SciTech Connect

    Cresson, J.

    2015-03-15

    We study the Sharma-Parthasarathy stochastic two-body problem introduced by Sharma and Parthasarathy in [“Dynamics of a stochastically perturbed two-body problem,” Proc. R. Soc. A 463, 979-1003 (2007)]. In particular, we focus on the preservation of some fundamental features of the classical two-body problem like the Hamiltonian structure and first integrals in the stochastic case. Numerical simulations are performed which illustrate the dynamical behaviour of the osculating elements as the semi-major axis, the eccentricity, and the pericenter. We also derive a stochastic version of Gauss’s equations in the planar case.

  17. Residue Specific and Chirality Dependent Interactions between Carbon Nanotubes and Flagellin.

    PubMed

    Macwan, Isaac G; Zhao, Zihe; Sobh, Omar T; Mukerji, Ishita; Dharmadhikari, Bhushan; Patra, Prabir K

    2016-01-01

    Flagellum is a lash-like cellular appendage found in many single-celled living organisms. The flagellin protofilaments contain 11-helix dual turn structure in a single flagellum. Each flagellin consists of four sub-domains - two inner domains (D0, D1) and two outer domains (D2, D3). While inner domains predominantly consist of α-helices, the outer domains are primarily beta sheets with D3. In flagellum, the outermost sub-domain is the only one that is exposed to the native environment. This study focuses on the interactions of the residues of D3 of an R-type flagellin with 5nm long chiral (5,15) and arm-chair (12,12) single-walled carbon nanotubes (SWNT) using molecular dynamics simulation. It presents the interactive forces between the SWNT and the residues of D3 from the perspectives of size and chirality of the SWNT. It is found that the metallic (arm-chair) SWNT interacts the most with glycine and threonine residues through van der Waals and hydrophobic interactions, whereas the semiconducting (chiral) SWNT interacts largely with the area of protein devoid of glycine by van der Waals, hydrophobic interactions, and hydrogen bonding. This indicates a crucial role that glycine plays in distinguishing metallic from semiconducting SWNTs.

  18. Residual Structures, Conformational Fluctuations, and Electrostatic Interactions in the Synergistic Folding of Two Intrinsically Disordered Proteins

    PubMed Central

    Zhang, Weihong; Ganguly, Debabani; Chen, Jianhan

    2012-01-01

    To understand the interplay of residual structures and conformational fluctuations in the interaction of intrinsically disordered proteins (IDPs), we first combined implicit solvent and replica exchange sampling to calculate atomistic disordered ensembles of the nuclear co-activator binding domain (NCBD) of transcription coactivator CBP and the activation domain of the p160 steroid receptor coactivator ACTR. The calculated ensembles are in quantitative agreement with NMR-derived residue helicity and recapitulate the experimental observation that, while free ACTR largely lacks residual secondary structures, free NCBD is a molten globule with a helical content similar to that in the folded complex. Detailed conformational analysis reveals that free NCBD has an inherent ability to substantially sample all the helix configurations that have been previously observed either unbound or in complexes. Intriguingly, further high-temperature unbinding and unfolding simulations in implicit and explicit solvents emphasize the importance of conformational fluctuations in synergistic folding of NCBD with ACTR. A balance between preformed elements and conformational fluctuations appears necessary to allow NCBD to interact with different targets and fold into alternative conformations. Together with previous topology-based modeling and existing experimental data, the current simulations strongly support an “extended conformational selection” synergistic folding mechanism that involves a key intermediate state stabilized by interaction between the C-terminal helices of NCBD and ACTR. In addition, the atomistic simulations reveal the role of long-range as well as short-range electrostatic interactions in cooperating with readily fluctuating residual structures, which might enhance the encounter rate and promote efficient folding upon encounter for facile binding and folding interactions of IDPs. Thus, the current study not only provides a consistent mechanistic understanding of

  19. General method to evaluate two-body integrals for relativistic atomic calculations

    NASA Astrophysics Data System (ADS)

    Ley-Koo, E.; Jáuregui, R.; Góngora-T., A.; Bunge, C. F.

    1993-03-01

    The method of Ley-Koo and Bunge [Phys. Rev. A 40, 1215 (1989)] to evaluate nonrelativistic atomic two-body integrals without a series expansion of the interaction function is extended to the relativistic case. Explicit and general formulas are obtained for the efficient evaluation or handling of atomic electron-electron integrals over bispinorial one-electron functions, including the electromagnetic interaction with retardation effects and the parity-nonconserving weak interaction in both the Yukawa and contact forms.

  20. Transition between random and collective behaviour in spectra generated by two-body forces

    NASA Astrophysics Data System (ADS)

    Cortes, A.; Haq, R. U.; Zuker, A. P.

    1982-08-01

    Monte Carlo calculations for the spectra of βHR + αHQ, a random two-body hamiltonian ( HR) augmented by an SU(3) interaction ( HQ) reveal a rapid transition at α ≈ β for spaces exhibiting a well developed rotational band for α ⪆ β and purely statistical behaviour for α ⪅ β.

  1. Fermi polaron in two dimensions: Importance of the two-body bound state

    SciTech Connect

    Klawunn, Michael; Recati, Alessio

    2011-09-15

    We investigate a single impurity interacting with a free two-dimensional atomic Fermi gas. The interaction between the impurity and the gas is characterized by an arbitrary attractive short-range potential, which, in two dimensions, always admits a two-particle bound state. We provide analytical expressions for the energy and the effective mass of the dressed impurity by including the two-body bound state, which is crucial for strong interactions, in the integral equation for the effective interaction. Using the same method, we also give the results for the polaron parameters in one and three dimensions and find good agreement with previous results. Thus, our relations can be used as a simple way to estimate the polaron parameters once the two-body bound state of the interaction potential is known.

  2. Interaction between dimer interface residues of native and mutated SOD1 protein: a theoretical study.

    PubMed

    Keerthana, S P; Kolandaivel, P

    2015-04-01

    Cu-Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein enzyme, used for the scavenging the superoxide radicals (O2 (-)) produced due to aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations have been identified and found to be in the homodimeric structure of SOD1. The enzyme has to be maintained in its dimeric state for the structural stability and enzymatic activity. From our investigation, we found that the mutations apart from the dimer interface residues are found to affect the dimer stability of protein and hence enhancing the aggregation and misfolding tendency of mutated protein. The homodimeric state of SOD1 is found to be held together by the non-covalent interactions. The molecular dynamics simulation has been used to study the hydrogen bond interactions between the dimer interface residues of the monomers in native and mutated forms of SOD1 in apo- and holo-states. The results obtained by this analysis reveal the fact that the loss of hydrogen bond interactions between the monomers of the dimer is responsible for the reduced stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer interface residues in native and mutated protein obtained by the molecular dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d) level of theory. The charge transfer between N-H···O interactions in the dimer interface residues were studied. The weak interaction between the monomers of the dimer accounts for the reduced dimerization and enhanced deformation energy in the mutated SOD1 protein.

  3. On the role of lysine residues in the bromophenol blue-albumin interaction.

    PubMed

    Trivedi, V D

    1997-06-01

    In order to explore the role of buried lysine residues of bovine serum albumin (BSA) in its interaction with bromophenol blue (BPB), three acetylated derivatives of albumin namely: 90%, 100% and 10%/chiefly having modification of buried lysine residues) were prepared by conventional and double modification techniques. The modification of lysine residues resulted in the change in conformation, as evidenced by the increase in Stokes radius from 3.55 nm (for native albumin) to 4.91 and 4.97 nm for 90% and 100% acetylated albumins, respectively. Modification of buried lysine residues (10% acetylated preparation) of albumin increased the Stokes radius up to 3.96 nm. The interaction of BPB with albumin preparations was studied spectrophotometrically at ionic strength 0.4 and at three different pH values i.e., 4.0, 6.0 and 8.0. There was decrease in BPB binding on increasing the modification. A decrease of 63% and 69% was noticed at pH 8.0 in 90% and 100% acetylated preparation, respectively. The 10% acetylated BSA preparation with minimum conformational changes also showed a significant decrease (31%) in BPB binding at pH 8.0. The change in Kd from 2.04 x 10(-6) M for native albumin to 5.41 x 10(-6) M for 100% acetylated albumin and 3.39 x 10(-6) M for 10% acetylated preparation at pH 8.0 confirmed the critical role of buried lysine residues in BPB-BSA interaction.

  4. Sulphur Atoms from Methionines Interacting with Aromatic Residues Are Less Prone to Oxidation.

    PubMed

    Aledo, Juan C; Cantón, Francisco R; Veredas, Francisco J

    2015-11-24

    Methionine residues exhibit different degrees of susceptibility to oxidation. Although solvent accessibility is a relevant factor, oxidation at particular sites cannot be unequivocally explained by accessibility alone. To explore other possible structural determinants, we assembled different sets of oxidation-sensitive and oxidation-resistant methionines contained in human proteins. Comparisons of the proteins containing oxidized methionines with all proteins in the human proteome led to the conclusion that the former exhibit a significantly higher mean value of methionine content than the latter. Within a given protein, an examination of the sequence surrounding the non-oxidized methionine revealed a preference for neighbouring tyrosine and tryptophan residues, but not for phenylalanine residues. However, because the interaction between sulphur atoms and aromatic residues has been reported to be important for the stabilization of protein structure, we carried out an analysis of the spatial interatomic distances between methionines and aromatic residues, including phenylalanine. The results of these analyses uncovered a new determinant for methionine oxidation: the S-aromatic motif, which decreases the reactivity of the involved sulphur towards oxidants.

  5. Sulphur Atoms from Methionines Interacting with Aromatic Residues Are Less Prone to Oxidation

    PubMed Central

    Aledo, Juan C.; Cantón, Francisco R.; Veredas, Francisco J.

    2015-01-01

    Methionine residues exhibit different degrees of susceptibility to oxidation. Although solvent accessibility is a relevant factor, oxidation at particular sites cannot be unequivocally explained by accessibility alone. To explore other possible structural determinants, we assembled different sets of oxidation-sensitive and oxidation-resistant methionines contained in human proteins. Comparisons of the proteins containing oxidized methionines with all proteins in the human proteome led to the conclusion that the former exhibit a significantly higher mean value of methionine content than the latter. Within a given protein, an examination of the sequence surrounding the non-oxidized methionine revealed a preference for neighbouring tyrosine and tryptophan residues, but not for phenylalanine residues. However, because the interaction between sulphur atoms and aromatic residues has been reported to be important for the stabilization of protein structure, we carried out an analysis of the spatial interatomic distances between methionines and aromatic residues, including phenylalanine. The results of these analyses uncovered a new determinant for methionine oxidation: the S-aromatic motif, which decreases the reactivity of the involved sulphur towards oxidants. PMID:26597773

  6. Randomizing the unfolded state of peptides (and proteins) by nearest neighbor interactions between unlike residues.

    PubMed

    Toal, Siobhan E; Kubatova, Nina; Richter, Christian; Linhard, Verena; Schwalbe, Harald; Schweitzer-Stenner, Reinhard

    2015-03-23

    To explore the influence of nearest neighbors on conformational biases in unfolded peptides, we combined vibrational and 2D NMR spectroscopy to obtain the conformational distributions of selected "GxyG" host-guest peptides in aqueous solution: GDyG, GSyG, GxLG, GxVG, where x/y=A, K, L, V. Large changes of conformational propensities were observed due to nearest-neighbor interactions, at variance with the isolated pair hypothesis. We found that protonated aspartic acid and serine lose their above-the-average preference for turn-like structures in favor of polyproline II (pPII) populations in the presence of neighbors with bulky side chains. Such residues also decrease the above-the-average pPII preference of alanine. These observations suggest that the underlying mechanism involves a disruption of the hydration shell. Thermodynamic analysis of (3) J(H(N) ,H(α) ) (T) data for each x,y residue reveals that modest changes in the conformational ensemble masks larger changes of enthalpy and entropy governing the pPII↔β equilibrium indicating a significant residue dependent temperature dependence of the peptides' conformational ensembles. These results suggest that nearest-neighbor interactions between unlike residues act as conformational randomizers close to the enthalpy-entropy compensation temperature, eliminating intrinsic biases in favor of largely balanced pPII/β dominated ensembles at physiological temperatures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Two-body relaxation in simulated cosmological haloes

    NASA Astrophysics Data System (ADS)

    El-Zant, Amr A.

    2006-08-01

    This paper aims to quantify, in a general manner that does not directly resort to large-scale calculations, discreteness effects acting on the dynamics of dark matter haloes forming in the context of cosmological simulations. By generalizing the standard formulation of two-body relaxation to the case when the size and mass distributions are variable, and parametrizing the time evolution using established empirical relations, we find that the dynamics of a million-particle halo is noise-dominated within the inner per cent of the final virial radius. Far larger particle numbers (~108) are required for the rms perturbations to the velocity to drop to the 10per cent level there. The radial scaling of the relaxation time is simple and strong: trelax ~r2, implying that numbers >>108 are required to faithfully model the very inner regions; artificial relaxation may thus constitute an important factor, contributing to the contradictory claims concerning the persistence of a power-law density cusp to the very centre. The cores of substructure haloes can be many relaxation times old. Since relaxation first causes their expansion before recontraction occurs, it may render them either more difficult or easier to disrupt, depending on their orbital parameters. This may modify the characteristics of the subhalo distribution; and if, as suggested by several authors, it is parent-satellite interactions that determine halo profiles, the overall structure of the system may be affected. We derive simple closed form formulae for the characteristic relaxation time of both parents and satellites, and an elementary argument deducing the weak N-scaling reported by Diemand et al. when the main contribution comes from relaxing subhaloes.

  8. Two-body physics in the Su-Schrieffer-Heeger model

    NASA Astrophysics Data System (ADS)

    Di Liberto, M.; Recati, A.; Carusotto, I.; Menotti, C.

    2016-12-01

    We consider two interacting bosons in a dimerized Su-Schrieffer-Heeger (SSH) lattice. We identify a rich variety of two-body states. In particular, for open boundary conditions and moderate interactions, edge bound states (EBS) are present even for the dimerization that does not sustain single-particle edge states. Moreover, for large values of the interactions, we find a breaking of the standard bulk-boundary correspondence. Based on the mapping of two interacting particles in one dimension onto a single particle in two dimensions, we propose an experimentally realistic coupled optical fibers setup as quantum simulator of the two-body SSH model. This setup is able to highlight the localization properties of the states as well as the presence of a resonant scattering mechanism provided by a bound state that crosses the scattering continuum, revealing the closed-channel population in real time and real space.

  9. Ligand Binding and Circular Permutation Modify Residue Interaction Network in DHFR

    PubMed Central

    Hu, Zengjian; Bowen, Donnell; Southerland, William M; del Sol, Antonio; Pan, Yongping; Nussinov, Ruth; Ma, Buyong

    2007-01-01

    Residue interaction networks and loop motions are important for catalysis in dihydrofolate reductase (DHFR). Here, we investigate the effects of ligand binding and chain connectivity on network communication in DHFR. We carry out systematic network analysis and molecular dynamics simulations of the native DHFR and 19 of its circularly permuted variants by breaking the chain connections in ten folding element regions and in nine nonfolding element regions as observed by experiment. Our studies suggest that chain cleavage in folding element areas may deactivate DHFR due to large perturbations in the network properties near the active site. The protein active site is near or coincides with residues through which the shortest paths in the residue interaction network tend to go. Further, our network analysis reveals that ligand binding has “network-bridging effects” on the DHFR structure. Our results suggest that ligand binding leads to a modification, with most of the interaction networks now passing through the cofactor, shortening the average shortest path. Ligand binding at the active site has profound effects on the network centrality, especially the closeness. PMID:17571919

  10. Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration.

    PubMed

    Mabrouk, Kamel; Ram, Narendra; Boisseau, Sylvie; Strappazzon, Flavie; Rehaim, Amel; Sadoul, Rémy; Darbon, Hervé; Ronjat, Michel; De Waard, Michel

    2007-10-01

    Maurocalcine (MCa) is a 33-amino acid residue peptide that was initially identified in the Tunisian scorpion Scorpio maurus palmatus. This peptide triggers interest for three main reasons. First, it helps unravelling the mechanistic basis of Ca(2+) mobilization from the sarcoplasmic reticulum because of its sequence homology with a calcium channel domain involved in excitation-contraction coupling. Second, it shows potent pharmacological properties because of its ability to activate the ryanodine receptor. Finally, it is of technological value because of its ability to carry cell-impermeable compounds across the plasma membrane. Herein, we characterized the molecular determinants that underlie the pharmacological and cell-penetrating properties of maurocalcine. We identify several key amino acid residues of the peptide that will help the design of cell-penetrating analogues devoid of pharmacological activity and cell toxicity. Close examination of the determinants underlying cell penetration of maurocalcine reveals that basic amino acid residues are required for an interaction with negatively charged lipids of the plasma membrane. Maurocalcine analogues that penetrate better have also stronger interaction with negatively charged lipids. Conversely, less effective analogues present a diminished ability to interact with these lipids. These findings will also help the design of still more potent cell penetrating analogues of maurocalcine.

  11. PAIRpred: partner-specific prediction of interacting residues from sequence and structure.

    PubMed

    Minhas, Fayyaz ul Amir Afsar; Geiss, Brian J; Ben-Hur, Asa

    2014-07-01

    We present a novel partner-specific protein-protein interaction site prediction method called PAIRpred. Unlike most existing machine learning binding site prediction methods, PAIRpred uses information from both proteins in a protein complex to predict pairs of interacting residues from the two proteins. PAIRpred captures sequence and structure information about residue pairs through pairwise kernels that are used for training a support vector machine classifier. As a result, PAIRpred presents a more detailed model of protein binding, and offers state of the art accuracy in predicting binding sites at the protein level as well as inter-protein residue contacts at the complex level. We demonstrate PAIRpred's performance on Docking Benchmark 4.0 and recent CAPRI targets. We present a detailed performance analysis outlining the contribution of different sequence and structure features, together with a comparison to a variety of existing interface prediction techniques. We have also studied the impact of binding-associated conformational change on prediction accuracy and found PAIRpred to be more robust to such structural changes than existing schemes. As an illustration of the potential applications of PAIRpred, we provide a case study in which PAIRpred is used to analyze the nature and specificity of the interface in the interaction of human ISG15 protein with NS1 protein from influenza A virus. Python code for PAIRpred is available at http://combi.cs.colostate.edu/supplements/pairpred/. © 2013 Wiley Periodicals, Inc.

  12. Sequence-based discrimination of protein-RNA interacting residues using a probabilistic approach.

    PubMed

    Pai, Priyadarshini P; Dash, Tirtharaj; Mondal, Sukanta

    2017-04-07

    Protein interactions with ribonucleic acids (RNA) are well-known to be crucial for a wide range of cellular processes such as transcriptional regulation, protein synthesis or translation, and post-translational modifications. Identification of the RNA-interacting residues can provide insights into these processes and aid in relevant biotechnological manipulations. Owing to their eventual potential in combating diseases and industrial production, several computational attempts have been made over years using sequence- and structure-based information. Recent comparative studies suggest that despite these developments, many problems are faced with respect to the usability, prerequisites, and accessibility of various tools, thereby calling for an alternative approach and perspective supplementation in the prediction scenario. With this motivation, in this paper, we propose the use of a simple-yet-efficient conditional probabilistic approach based on the application of local occurrence of amino acids in the interacting region in a non-numeric sequence feature space, for discriminating between RNA interacting and non-interacting residues. The proposed method has been meticulously tested for robustness using a cross-estimation method showing MCC of 0.341 and F- measure of 66.84%. Upon exploring large scale applications using benchmark datasets available to date, this approach showed an encouraging performance comparable with the state-of-art. The software is available at https://github.com/ABCgrp/DORAEMON. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Nonnatural protein–protein interaction-pair design by key residues grafting

    PubMed Central

    Liu, Sen; Liu, Shiyong; Zhu, Xiaolei; Liang, Huanhuan; Cao, Aoneng; Chang, Zhijie; Lai, Luhua

    2007-01-01

    Protein–protein interface design is one of the most exciting fields in protein science; however, designing nonnatural protein–protein interaction pairs remains difficult. In this article we report a de novo design of a nonnatural protein–protein interaction pair by scanning the Protein Data Bank for suitable scaffold proteins that can be used for grafting key interaction residues and can form stable complexes with the target protein after additional mutations. Using our design algorithm, an unrelated protein, rat PLCδ1-PH (pleckstrin homology domain of phospholipase C-δ1), was successfully designed to bind the human erythropoietin receptor (EPOR) after grafting the key interaction residues of human erythropoietin binding to EPOR. The designed mutants of rat PLCδ1-PH were expressed and purified to test their binding affinities with EPOR. A designed triple mutation of PLCδ1-PH (ERPH1) was found to bind EPOR with high affinity (KD of 24 nM and an IC50 of 5.7 μM) both in vitro and in a cell-based assay, respectively, although the WT PLCδ1-PH did not show any detectable binding under the assay conditions. The in vitro binding affinities of the PLCδ1-PH mutants correlate qualitatively to the computational binding affinities, validating the design and the protein–protein interaction model. The successful practice of finding a proper protein scaffold and making it bind with EPOR demonstrates a prospective application in protein engineering targeting protein–protein interfaces. PMID:17372228

  14. Deciphering Key Residues Involved in the Virulence-promoting Interactions between Streptococcus pneumoniae and Human Plasminogen.

    PubMed

    Moreau, Christophe; Terrasse, Rémi; Thielens, Nicole M; Vernet, Thierry; Gaboriaud, Christine; Di Guilmi, Anne Marie

    2017-02-10

    Bacterial pathogens recruit circulating proteins to their own surfaces, co-opting the host protein functions as a mechanism of virulence. Particular attention has focused on the binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytoplasmic enzyme that appears on the cell surface in this moonlighting role. Although Plg typically binds to these receptors via several lysine-binding domains, the specific interactions that occur have not been documented in all cases. However, identification of the relevant residues could help define strategies for mitigating the virulence of important human pathogens, such as Streptococcus pneumoniae (Sp). To shed light on this question, we have described a combination of peptide-spot array screening, competition and SPR assays, high-resolution crystallography, and mutational analyses to characterize the interaction between SpGAPDH and Plg. We identified three SpGAPDH lysine residues that were instrumental in defining the kinetic and thermodynamic parameters of the interaction. Altogether, the integration of the data presented in this work allows us to propose a structural model for the molecular interaction of the SpGAPDH-Plg complex.

  15. The RING 2.0 web server for high quality residue interaction networks

    PubMed Central

    Piovesan, Damiano; Minervini, Giovanni; Tosatto, Silvio C.E.

    2016-01-01

    Residue interaction networks (RINs) are an alternative way of representing protein structures where nodes are residues and arcs physico–chemical interactions. RINs have been extensively and successfully used for analysing mutation effects, protein folding, domain–domain communication and catalytic activity. Here we present RING 2.0, a new version of the RING software for the identification of covalent and non-covalent bonds in protein structures, including π–π stacking and π–cation interactions. RING 2.0 is extremely fast and generates both intra and inter-chain interactions including solvent and ligand atoms. The generated networks are very accurate and reliable thanks to a complex empirical re-parameterization of distance thresholds performed on the entire Protein Data Bank. By default, RING output is generated with optimal parameters but the web server provides an exhaustive interface to customize the calculation. The network can be visualized directly in the browser or in Cytoscape. Alternatively, the RING-Viz script for Pymol allows visualizing the interactions at atomic level in the structure. The web server and RING-Viz, together with an extensive help and tutorial, are available from URL: http://protein.bio.unipd.it/ring. PMID:27198219

  16. The RING 2.0 web server for high quality residue interaction networks.

    PubMed

    Piovesan, Damiano; Minervini, Giovanni; Tosatto, Silvio C E

    2016-07-08

    Residue interaction networks (RINs) are an alternative way of representing protein structures where nodes are residues and arcs physico-chemical interactions. RINs have been extensively and successfully used for analysing mutation effects, protein folding, domain-domain communication and catalytic activity. Here we present RING 2.0, a new version of the RING software for the identification of covalent and non-covalent bonds in protein structures, including π-π stacking and π-cation interactions. RING 2.0 is extremely fast and generates both intra and inter-chain interactions including solvent and ligand atoms. The generated networks are very accurate and reliable thanks to a complex empirical re-parameterization of distance thresholds performed on the entire Protein Data Bank. By default, RING output is generated with optimal parameters but the web server provides an exhaustive interface to customize the calculation. The network can be visualized directly in the browser or in Cytoscape. Alternatively, the RING-Viz script for Pymol allows visualizing the interactions at atomic level in the structure. The web server and RING-Viz, together with an extensive help and tutorial, are available from URL: http://protein.bio.unipd.it/ring. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Automated detection and quantification of residual brain tumor using an interactive computer-aided detection scheme

    NASA Astrophysics Data System (ADS)

    Gaffney, Kevin P.; Aghaei, Faranak; Battiste, James; Zheng, Bin

    2017-03-01

    Detection of residual brain tumor is important to evaluate efficacy of brain cancer surgery, determine optimal strategy of further radiation therapy if needed, and assess ultimate prognosis of the patients. Brain MR is a commonly used imaging modality for this task. In order to distinguish between residual tumor and surgery induced scar tissues, two sets of MRI scans are conducted pre- and post-gadolinium contrast injection. The residual tumors are only enhanced in the post-contrast injection images. However, subjective reading and quantifying this type of brain MR images faces difficulty in detecting real residual tumor regions and measuring total volume of the residual tumor. In order to help solve this clinical difficulty, we developed and tested a new interactive computer-aided detection scheme, which consists of three consecutive image processing steps namely, 1) segmentation of the intracranial region, 2) image registration and subtraction, 3) tumor segmentation and refinement. The scheme also includes a specially designed and implemented graphical user interface (GUI) platform. When using this scheme, two sets of pre- and post-contrast injection images are first automatically processed to detect and quantify residual tumor volume. Then, a user can visually examine segmentation results and conveniently guide the scheme to correct any detection or segmentation errors if needed. The scheme has been repeatedly tested using five cases. Due to the observed high performance and robustness of the testing results, the scheme is currently ready for conducting clinical studies and helping clinicians investigate the association between this quantitative image marker and outcome of patients.

  18. Conserved residues of the human mitochondrial holocytochrome c synthase mediate interactions with heme.

    PubMed

    Babbitt, Shalon E; San Francisco, Brian; Bretsnyder, Eric C; Kranz, Robert G

    2014-08-19

    C-type cytochromes are distinguished by the covalent attachment of a heme cofactor, a modification that is typically required for its subsequent folding, stability, and function. Heme attachment takes place in the mitochondrial intermembrane space and, in most eukaryotes, is mediated by holocytochrome c synthase (HCCS). HCCS is the primary component of the eukaryotic cytochrome c biogenesis pathway, known as System III. The catalytic function of HCCS depends on its ability to coordinate interactions between its substrates: heme and cytochrome c. Recent advancements in the recombinant expression and purification of HCCS have facilitated comprehensive analyses of the roles of conserved residues in HCCS, as demonstrated in this study. Previously, we proposed a four-step model describing HCCS-mediated cytochrome c assembly, identifying a conserved histidine residue (His154) as an axial ligand to the heme iron. In this study, we performed a systematic mutational analysis of 17 conserved residues in HCCS, and we provide evidence that the enzyme contains two heme-binding domains. Our data indicate that heme contacts mediated by residues within these domains modulate the dynamics of heme binding and contribute to the stability of the HCCS-heme-cytochrome c steady state ternary complex. While some residues are essential for initial heme binding (step 1), others impact the subsequent release of the holocytochrome c product (step 4). Certain HCCS mutants that were defective in heme binding were corrected for function by exogenous aminolevulinic acid (ALA, the precursor to heme). This chemical "correction" supports the proposed role of heme binding for the corresponding residues.

  19. Conserved Residues of the Human Mitochondrial Holocytochrome c Synthase Mediate Interactions with Heme

    PubMed Central

    2015-01-01

    C-type cytochromes are distinguished by the covalent attachment of a heme cofactor, a modification that is typically required for its subsequent folding, stability, and function. Heme attachment takes place in the mitochondrial intermembrane space and, in most eukaryotes, is mediated by holocytochrome c synthase (HCCS). HCCS is the primary component of the eukaryotic cytochrome c biogenesis pathway, known as System III. The catalytic function of HCCS depends on its ability to coordinate interactions between its substrates: heme and cytochrome c. Recent advancements in the recombinant expression and purification of HCCS have facilitated comprehensive analyses of the roles of conserved residues in HCCS, as demonstrated in this study. Previously, we proposed a four-step model describing HCCS-mediated cytochrome c assembly, identifying a conserved histidine residue (His154) as an axial ligand to the heme iron. In this study, we performed a systematic mutational analysis of 17 conserved residues in HCCS, and we provide evidence that the enzyme contains two heme-binding domains. Our data indicate that heme contacts mediated by residues within these domains modulate the dynamics of heme binding and contribute to the stability of the HCCS–heme–cytochrome c steady state ternary complex. While some residues are essential for initial heme binding (step 1), others impact the subsequent release of the holocytochrome c product (step 4). Certain HCCS mutants that were defective in heme binding were corrected for function by exogenous aminolevulinic acid (ALA, the precursor to heme). This chemical “correction” supports the proposed role of heme binding for the corresponding residues. PMID:25054239

  20. Interacting residues in an activated state of a G protein-coupled receptor.

    PubMed

    Lee, Yong-Hun; Naider, Fred; Becker, Jeffrey M

    2006-01-27

    Ste2p, the G protein-coupled receptor (GPCR) for the tridecapeptide pheromone alpha-factor of Saccharomyces cerevisiae, was used as a model GPCR to investigate the role of specific residues in the resting and activated states of the receptor. Using a series of biological and biochemical analyses of wild-type and site-directed mutant receptors, we identified Asn(205) as a potential interacting partner with the Tyr(266) residue. An N205H/Y266H double mutant showed pH-dependent functional activity, whereas the N205H receptor was non-functional and the Y266H receptor was partially active indicating that the histidine 205 and 266 residues interact in an activated state of the receptor. The introduction of N205K or Y266D mutations into the P258L/S259L constitutively active receptor suppressed the constitutive activity; in contrast, the N205K/Y266D/P258L/S259L quadruple mutant was fully constitutively active, again indicating an interaction between residues at the 205 and 206 positions in the receptor-active state. To further test this interaction, we introduced the N205C/Y266C, F204C/Y266C, and N205C/A265C double mutations into wild-type and P258L/S259L constitutively active receptors. After trypsin digestion, we found that a disulfide-cross-linked product, with the molecular weight expected for a receptor fragment with a cross-link between N205C and Y266C, formed only in the N205C/Y266C constitutively activated receptor. This study represents the first experimental demonstration of an interaction between specific residues in an active state, but not the resting state, of Ste2p. The information gained from this study should contribute to an understanding of the conformational differences between resting and active states in GPCRs.

  1. Two-Body and Three-Body Atomic Recombination Reactions.

    ERIC Educational Resources Information Center

    Alvarino, Jose M.; Martinez, E.

    1983-01-01

    Discusses how, in some circumstances, a two-body reaction (association in absence of a third body) is the only possible association, and how reactions proceed in this case. Taking competition between two/three-body reactions into account, considers relative importance of such combinations and conditions under which the former can be competitive.…

  2. Two-Body and Three-Body Atomic Recombination Reactions.

    ERIC Educational Resources Information Center

    Alvarino, Jose M.; Martinez, E.

    1983-01-01

    Discusses how, in some circumstances, a two-body reaction (association in absence of a third body) is the only possible association, and how reactions proceed in this case. Taking competition between two/three-body reactions into account, considers relative importance of such combinations and conditions under which the former can be competitive.…

  3. Stochastic perturbation of the two-body problem

    NASA Astrophysics Data System (ADS)

    Cresson, J.; Pierret, F.; Puig, B.

    2013-11-01

    We study the impact of a stochastic perturbation on the classical two-body problem in particular concerning the preservation of first integrals and the Hamiltonian structure. Numerical simulations are performed which illustrate the dynamical behavior of the osculating elements as the semi-major axis, the eccentricity and the pericenter. We also derive a stochastic version of Gauss's equations in the planar case.

  4. Identification of guanine exchange factor key residues involved in exchange activity and Ras interaction.

    PubMed

    Camus, C; Hermann-Le Denmat, S; Jacquet, M

    1995-09-07

    We have carried out a functional analysis of the human HGRF55 exchange factor in the yeast Saccharomyces cerevisiae. Twelve residues conserved among most of all known guanine exchange factors (GEFs) have been independently changed to alanine. Taking advantage of the ability of Hgrf55p to replace the yeast Cdc25p exchange factor, and using the two-hybrid system with RAS2ala22 allele, we have identified key residues for the interaction with Ras and/or its activation. Substitution of arginine 392 to alanine leads to a complete loss of interaction with Ras, though the protein remains stable. Substitution of Asp266 or Arg359 to alanine results in inactive proteins at 39 degrees C, still able however to interact with Ras. The other charged-to-alanine substitutions led to no detectable phenotype when present alone but most of them dramatically increased the temperature sensitive phenotype observed with [Asp266Ala] substitution. Surprisingly, the cysteine to alanine substitution in the highly conserved PCVPF/Y motif proved to be without effect, suggesting that the sulfhydryl group is not essential for stability or interaction with Ras.

  5. Development of helix-based vasoactive intestinal peptide analogues: identification of residues required for receptor interaction.

    PubMed

    Musso, G F; Patthi, S; Ryskamp, T C; Provow, S; Kaiser, E T; Veliçelebi, G

    1988-10-18

    Several VIP analogues have been designed on the basis of the hypothesis that the region from residue 6 to residue 28 forms a pi-helical structure when bound to membrane receptors. An empirical approach for the design and construction of analogues based upon distribution frequency and structural homology with several sequence-related peptides is presented. Five peptides were designed, synthesized, and analyzed. One analogue, model 5, containing the native hydrophobic and an altered hydrophilic surface, was an effective VIP agonist in both binding to rat lung membrane receptors (KD1 = 11 +/- 8 pM, KD2 = 6.4 +/- 0.2 nM; VIP KD1 = 21 +/- 13 pM, KD2 = 1.8 +/- 0.6 nM) and stimulation of amylase release from guinea pig pancreatic acini (ED50 = 90 pM; VIP ED50 = 27 pM). The four other analogues were considerably less potent than VIP, yet retained full intrinsic activity. Our results showed that the hydrophobic surface of this helical domain (residues 6-28) contains amino acids important for interaction with receptors, whereas amino acid residues on the hydrophilic surface do not seem to participate strongly in receptor binding or signal transduction. Furthermore, on the basis of high-affinity binding, the stimulation of amylase release in pancreatic acini appears to be coupled to the higher affinity receptors. These results suggest that an approach based on the construction of putative pi-helical structures can be applied to the design of biologically active analogues of VIP. Thus, we have identified several residues within the VIP sequence that are critical for receptor binding using this approach.

  6. Organomineral interactions as an important mechanism for stabilisation of bacterial residues in soil

    NASA Astrophysics Data System (ADS)

    Miltner, Anja; Achtenhagen, Jan; Kästner, Matthias

    2017-04-01

    Although plant material is the original input of organic matter to soils, microbial residues have been identified to contribute to a large extent to soil organic matter. However, until now it is unclear how microbial residues are stabilised in soil and protected from degradation. We hypothesised that organomineral interactions, in particular encrustation by oxides, may play an important role, which might vary depending on environmental conditions, e.g. redox potential. Therefore we produced 14C-labelled Escherichia coli cells and cell envelope fragments and coprecipitated these materials with Fe oxide or Al oxide. Mineral-free (control) and mineral-encrusted bacterial residues were incubated for 345 days at 20˚ C under either oxic or oxygen-limited conditions, and mineralisation was quantified by scintillation counting of the CO2 produced during incubation. Oxygen limitation was achieved by first exchanging the atmosphere in the incubation vessels with dinitrogen gas. After 100 days of incubation, the anoxic treatments were waterlogged to further decrease the redox potential, and after 290 days, glucose and nutrients were supplied to all treatments in order to foster microbial activity and consumption of electron acceptors. The mineralisation curves were fitted by double-exponential (0-100 days), first-order kinetic (100-290 days) and linear (290-345 days) models. The model parameters were tested for significant differences between the treatments by three-way ANOVA with post-hoc Bonferroni t-test. We found that encrustation by the oxides significantly reduced mineralisation of the bacterial residues. This effect was inversed by reductive dissolution of Fe oxides after substrate and nutrient addition to the oxygen-limited treatments, suggesting a significant role of the encrustation in stabilisation of the bacterial residues. We also observed that bacterial cell envelope fragments were generally slightly more resistant to mineralisation than whole cells. The

  7. RANS Simulation of the Heave Response of a Two-Body Floating Point Wave Absorber: Preprint

    SciTech Connect

    Yu, Y.; Li, Y.

    2011-03-01

    A preliminary study on a two-body floating wave absorbers is presented in this paper. A Reynolds-Averaged Navier-Stokes computational method is applied for analyzing the hydrodynamic heave response of the absorber in operational wave conditions. The two-body floating wave absorber contains a float section and a submerged reaction section. For validation purposes, our model is first assumed to be locked. The two sections are forced to move together with each other. The locked single body model is used in a heave decay test, where the RANS result is validated with the experimental measurement. For the two-body floating point absorber simulation, the two sections are connected through a mass-spring-damper system, which is applied to simulate the power take-off mechanism under design wave conditions. Overall, the details of the flow around the absorber and its nonlinear interaction with waves are investigated, and the power absorption efficiency of the two-body floating wave absorber in waves with a constant value spring-damper system is examined.

  8. Residues Critical for Duck Hepatitis B Virus Neutralization Are Involved in Host Cell Interaction

    PubMed Central

    Sunyach, Claire; Rollier, Christine; Robaczewska, Magdalena; Borel, Christelle; Barraud, Luc; Kay, Alan; Trépo, Christian; Will, Hans; Cova, Lucyna

    1999-01-01

    To date, no detailed analysis of the neutralization properties of duck hepatitis B virus (DHBV) has been reported, and it is not clear whether any of the known neutralization epitopes correspond to the viral receptor binding site or to sequences involved in the cell entry pathway. We demonstrate here that antibodies directed against two overlapping peptides (amino acids 83 to 97 and 93 to 107), covering the sequences of most DHBV pre-S neutralizing epitopes, both inhibit virus binding to primary duck hepatocytes and neutralize virus infectivity. An extensive mutagenesis of the motif 88WTP90, which is the shortest sequence of the epitope recognized by the virus-neutralizing monoclonal antibody (MAb) 900 was performed in order to define the amino acids involved in these interactions. Single point mutations within this epitope affected neither virus replication nor infectivity but abolished virus neutralization by MAb 900 completely. Interestingly, mutants with two and three consecutive residue replacements (SIP and SIH) within this epitope retained replication competence but were no longer infectious. The loss of infectivity of SIH and SIP mutant particles was associated with significantly reduced binding to primary duck hepatocytes and could be rescued by trans complementation with wild-type pre-S protein. Taken together, these results indicate that each amino acid of the DHBV pre-S sequence 88WTP90 is critical for recognition by the neutralizing MAb 900 and that replacement of the first two or all three residues strongly reduces virus interaction with hepatocytes and abrogates infectivity. These data imply that the motif 88WTP90 contains key residues which are critical for interaction with both the neutralizing MAb and the host cell. PMID:10074101

  9. Random-phase-approximation calculations and residual interactions in the sigmatau channel

    SciTech Connect

    Cohen, J.

    1986-05-01

    We compare numerical results for renormalized spin-isospin matrix elements within the random phase approximation. Extended calculations are carried out for a pionlike excitation in a finite nucleus; the effects of contact versus momentum-dependent residual interactions, and of ..delta..-h configurations, are demonstrated. We point out the implications of our results on nuclear structure calculations, where such effects are sometimes neglected. The role of the finite geometry of the system is crucial in determining the features of the spin-isospin responses. We emphasize that a crucial test of the theory can only be achieved through a direct comparison of the longitudinal and transverse channels.

  10. Relative displacement measurements for two-body problems

    NASA Technical Reports Server (NTRS)

    Post, D.; Czarnek, R.; Wood, J.; Joh, D.

    1985-01-01

    While high-sensitivity moire interferometry is very effective for displacement measurements in continuous bodies, special difficulties arise with two-body problems. Fringes may become discontinuous at the boundary between the bodies and as a result the relative displacements cannot be extracted from the fringe patterns. In this work, flexible bridges are used between the bodies to provide a continuous path for fringe counting. The bridges are made of relatively low modulus material and have a low stiffness geometry, such that they deform under minimal load. The experimental methods used for obtaining relative displacement measurements in two-body problems are described for the two cases; dovetail joint in turbo-machinery, and thick adherend lap joint.

  11. On the potential energy in a gravitationally bound two-body system

    NASA Astrophysics Data System (ADS)

    Wilhelm, Klaus; Dwivedi, Bhola N.

    2015-01-01

    The potential energy problem in a gravitationally bound two-body system is studied in the framework of a recently proposed impact model of gravity (Wilhelm et al., 2013). The concept of a closed system has been modified, before the physical processes resulting in the liberation of the potential energy can be described. The energy is extracted from the background flux of hypothetical interaction entities.

  12. Symmetries of Mücket-Treder's two-body problem

    NASA Astrophysics Data System (ADS)

    Mioc, V.

    The two-body problem associated to the classical potential field proposed by Mücket and Treder (1977) is considered from the only standpoint of symmetries. The corresponding vector field in Hamiltonian or standard polar coordinates presents nice symmetries that form eight-element symmetric Abelian groups endowed with an idempotent structure. Expressed in Levi-Civita coordinates, the problem exhibits a sixteen-element group of symmetries, also Abelian and presenting an idempotent structure.

  13. Global flow in the generalized Buckingham's two-body problem

    NASA Astrophysics Data System (ADS)

    Popescu, E.; Pricopi, D.

    2017-04-01

    In this paper, we consider the generalized Buckingham potential. Using the McGehee's regularizing transformations, we study the global flow for the two-body problem associated to this potential. By making vary the angular momentum constant in the three cases of negative, zero, and positive energy, we analyze all possible situations. In each case, we obtain the global flow of the problem, exhibiting a great variety of orbits. All phase portraits are interpreted in terms of physical trajectories.

  14. Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis

    PubMed Central

    Matsui, Yusuke; Shindo, Keisuke; Nagata, Kayoko; Io, Katsuhiro; Tada, Kohei; Iwai, Fumie; Kobayashi, Masayuki; Kadowaki, Norimitsu; Harris, Reuben S; Takaori-Kondo, Akifumi

    2014-01-01

    Vif is essential for HIV-1 replication in T cells and macrophages. Vif recruits a host ubiquitin ligase complex to promote proteasomal degradation of the APOBEC3 restriction factors by poly-ubiquitination. The cellular transcription cofactor CBFβ is required for Vif function by stabilizing the Vif protein and promoting recruitment of a cellular Cullin5-RING ubiquitin ligase complex. Interaction between Vif and CBFβ is a promising therapeutic target, but little is known about the interfacial residues. We now demonstrate that Vif conserved residues E88/W89 are crucial for CBFβ binding. Substitution of E88/W89 to alanines impaired binding to CBFβ, degradation of APOBEC3, and virus infectivity in the presence of APOBEC3 in single-cycle infection. In spreading infection, NL4-3 with Vif E88A/W89A mutation replicated comparably to wild-type virus in permissive CEM-SS cells, but not in multiple APOBEC3 expressing non-permissive CEM cells. These results support a model in which HIV-1 Vif residues E88/W89 may participate in binding CBFβ. PMID:24418540

  15. Lysine residues of ABCA1 are required for the interaction with apoA-I.

    PubMed

    Nagao, Kohjiro; Kimura, Yasuhisa; Ueda, Kazumitsu

    2012-03-01

    ATP-binding cassette protein A1 (ABCA1) plays a pivotal role in cholesterol homeostasis by generating high-density lipoprotein (HDL). Apolipoprotein A-I (apoA-I), a lipid acceptor for ABCA1, reportedly interacts with ABCA1. However, it has also been proposed that apoA-I interacts with ABCA1-generated special domains on the plasma membrane, but apart from ABCA1, and solubilizes membrane lipids. To determine the importance of the apoA-I-ABCA1 interaction in HDL formation, the electrostatic interaction between apoA-I and ABCA1, which mediates the interaction between apoB100 in low-density lipoprotein particles (LDL) and LDL receptor, was analyzed. The apoA-I binding to ABCA1 and the cross-linking between them were inhibited by the highly charged molecules heparin and poly-L-lysine. Treating cells with membrane impermeable reagents that specifically react with primary amino groups abolished the interaction between apoA-I and ABCA1. However, these reagents did not affect the characteristic tight ATP binding to ABCA1. These results suggest that lysine residues in the extracellular domains of ABCA1 contribute to the interaction with apoA-I. The electrostatic interaction between ABCA1 and apoA-I is predicted to be the first step in HDL formation. This article is part of a Special Issue entitled Advances in high density lipoprotein formation and metabolism: a tribute to John F. Oram (1945-2010).

  16. Structural Evolution in Atomic Nuclei: Residual Interactions, Quantum Phase Transitions and the Emergence of Collectivity

    SciTech Connect

    Casten, R. F.

    2007-10-26

    A synoptic view of the evolution of structure with Z and N in nuclei is beginning to emerge from the confiuence of new experimental results on phase transitional behavior, newly proposed many-body symmetries for critical point nuclei, a new generation of solvable collective models, powerful approaches to viewing the systematics of nuclear properties based on simple models of residual interactions, and advances in microscopic calculations of medium mass and heavy nuclei. A recent compilation of nuclear masses has contributed by permitting empirical extractions of new p-n interaction strengths of the last protons with the last neutrons in many nuclei across the nuclear chart. A number of these developments will be discussed with an eye to the opportunities and challenges they provide for the future, especially in the era of next-generation exotic beam facihties throughout the world.

  17. Conserved Cysteine Residues Provide a Protein-Protein Interaction Surface in Dual Oxidase (DUOX) Proteins*

    PubMed Central

    Meitzler, Jennifer L.; Hinde, Sara; Bánfi, Botond; Nauseef, William M.; Ortiz de Montellano, Paul R.

    2013-01-01

    Intramolecular disulfide bond formation is promoted in oxidizing extracellular and endoplasmic reticulum compartments and often contributes to protein stability and function. DUOX1 and DUOX2 are distinguished from other members of the NOX protein family by the presence of a unique extracellular N-terminal region. These peroxidase-like domains lack the conserved cysteines that confer structural stability to mammalian peroxidases. Sequence-based structure predictions suggest that the thiol groups present are solvent-exposed on a single protein surface and are too distant to support intramolecular disulfide bond formation. To investigate the role of these thiol residues, we introduced four individual cysteine to glycine mutations in the peroxidase-like domains of both human DUOXs and purified the recombinant proteins. The mutations caused little change in the stabilities of the monomeric proteins, supporting the hypothesis that the thiol residues are solvent-exposed and not involved in disulfide bonds that are critical for structural integrity. However, the ability of the isolated hDUOX1 peroxidase-like domain to dimerize was altered, suggesting a role for these cysteines in protein-protein interactions that could facilitate homodimerization of the peroxidase-like domain or, in the full-length protein, heterodimeric interactions with a maturation protein. When full-length hDUOX1 was expressed in HEK293 cells, the mutations resulted in decreased H2O2 production that correlated with a decreased amount of the enzyme localized to the membrane surface rather than with a loss of activity or with a failure to synthesize the mutant proteins. These results support a role for the cysteine residues in intermolecular disulfide bond formation with the DUOX maturation factor DUOXA1. PMID:23362256

  18. Interaction of 18-residue peptides derived from amphipathic helical segments of globular proteins with model membranes.

    PubMed

    Sivakamasundari, Chandrasekaran; Nagaraj, Ramakrishnan

    2009-06-01

    We investigated the interaction of six 18-residue peptides derived from amphipathic helical segments of globular proteins with model membranes. The net charge of the peptides at neutral pH varies from -1 to +6. Circular dichroism spectra indicate that peptides with a high net positive charge tend to fold into a helical conformation in the presence of negatively charged lipid vesicles. In helical conformation, their average hydrophobic moment and hydrophobicity would render them surface-active. The composition of amino acids on the polar face of the helix in the peptides is considerably different. The peptides show variations in their ability to permeabilise zwitterionic and anionic lipid vesicles. Whereas increased net positive charge favours greater permeabilisation, the distribution of charged residues in the polar face also plays a role in determining membrane activity. The distribution of amino acids in the polar face of the helix in the peptides that were investigated do not fall into the canonical classes described. Amphipathic helices, which are part of proteins, with a pattern of amino acid distribution different from those observed in class L, A and others, could help in providing newer insights into peptide-membrane interactions.

  19. Two-body bound and edge states in the extended SSH Bose-Hubbard model

    NASA Astrophysics Data System (ADS)

    Di Liberto, M.; Recati, A.; Carusotto, I.; Menotti, C.

    2017-07-01

    We study the bosonic two-body problem in a Su-Schrieffer-Heeger dimerized chain with on-site and nearest-neighbor interactions. We find two classes of bound states. The first, similar to the one induced by on-site interactions, has its center of mass on the strong link, whereas the second, existing only thanks to nearest-neighbor interactions, is centered on the weak link. We identify energy crossings between these states and analyse them using exact diagonalization and perturbation theory. In the presence of open boundary conditions, novel strongly-localized edge-bound states appear in the spectrum as a consequence of the interplay between lattice geometry, on-site and nearest-neighbor interactions. Contrary to the case of purely on-site interactions, such EBS persist even in the strongly interacting regime.

  20. Two-body quantum propagation in arbitrary potentials

    NASA Astrophysics Data System (ADS)

    Grasselli, Federico; Bertoni, Andrea; Goldoni, Guido

    2016-08-01

    We have implemented a unitary, numerically exact, Fourier split step method, based on a proper Suzuki-Trotter factorization of the quantum evolution operator, to propagate a two-body complex in arbitrary external potential landscapes taking into account exactly the internal structure. We have simulated spatially indirect Wannier-Mott excitons - optically excited electron-hole pairs with the two charges confined to different layers of a semiconductor heterostructure with prototypical 1D and 2D potentials emphasizing the effects of the internal dynamics and the insufficiency of mean-field methods in this context.

  1. Efimov pathology in effective two-body system

    SciTech Connect

    Kroeger, H.; Perne, R.

    1980-01-01

    Amado and Greenwood have shown that there is no Efimov effect for four or more particles. The present authors use an (n-1)-fold successive separable approximation (nssa) to the general n-body operator identities. They find that for the conditions considered the necessary condition for the existence of an infinite number of n-body bound levels (n > or = 4) is not violated. The nssa reduces the n-body to an effective two-body phase space. It is concluded that the appearance of the Efimov effect is not restricted to three-body systems. (RWR)

  2. Quasi-two-body decays B → Kρ → Kππ in perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Wang, Wen-Fei; Li, Hsiang-nan

    2016-12-01

    We analyze the quasi-two-body decays B → Kρ → Kππ in the perturbative QCD (PQCD) approach, in which final-state interactions between the pions in the resonant regions associated with the P-wave states ρ (770) and ρ‧ (1450) are factorized into two-pion distribution amplitudes. Adopting experimental inputs for the time-like pion form factors involved in two-pion distribution amplitudes, we calculate branching ratios and direct CP asymmetries of the B → Kρ (770) , Kρ‧ (1450) → Kππ modes. It is shown that agreement of theoretical results with data can be achieved, through which Gegenbauer moments of the P-wave two-pion distribution amplitudes are determined. The consistency between the three-body and two-body analyses of the B → Kρ (770) → Kππ decays supports the PQCD factorization framework for exclusive hadronic B meson decays.

  3. Constraining the leading weak axial two-body current by SNO and Super-K

    SciTech Connect

    Chen, Jiunn-Wei; Heeger, Karsten M.; Robertson, R.G. Hamish

    2002-10-24

    We analyze the Sudbury Neutrino Observatory (SNO) and Super-Kamiokande (SK) data on charged current (CC), neutral current (NC) and neutrino electron elastic scattering (ES) reactions to constrain the leading weak axial two-body current parameterized by L{sub 1A}. This two-body current is the dominant uncertainty of every low energy weak interaction deuteron breakup process, including SNO's CC and NC reactions. Our method shows that the theoretical inputs to SNO's determination of the CC and NC fluxes can be self-calibrated, be calibrated by SK, or be calibrated by reactor data. The only assumption made is that the total flux of active neutrinos has the standard {sup 8}B spectral shape (but distortions in the electron neutrino spectrum are allowed). We show that SNO's conclusion about the inconsistency of the no-flavor-conversion hypothesis does not contain significant theoretical uncertainty, and we determine the magnitude of the active solar neutrino flux.

  4. Surface-exposed amino acid residues of HPV16 L1 protein mediating interaction with cell surface heparan sulfate.

    PubMed

    Knappe, Maren; Bodevin, Sabrina; Selinka, Hans-Christoph; Spillmann, Dorothe; Streeck, Rolf E; Chen, Xiaojiang S; Lindahl, Ulf; Sapp, Martin

    2007-09-21

    Efficient infection of cells by human papillomaviruses (HPVs) and pseudovirions requires primary interaction with cell surface proteoglycans with apparent preference for species carrying heparan sulfate (HS) side chains. To identify residues contributing to virus/cell interaction, we performed point mutational analysis of the HPV16 major capsid protein, L1, targeting surface-exposed amino acid residues. Replacement of lysine residues 278, 356, or 361 for alanine reduced cell binding and infectivity of pseudovirions. Various combinations of these amino acid exchanges further decreased cell attachment and infectivity with residual infectivity of less than 5% for the triple mutant, suggesting that these lysine residues cooperate in HS binding. Single, double, or triple exchanges for arginine did not impair infectivity, demonstrating that interaction is dependent on charge distribution rather than sequence-specific. The lysine residues are located within a pocket on the capsomere surface, which was previously proposed as the putative receptor binding site. Fab fragments of binding-neutralizing antibody H16.56E that recognize an epitope directly adjacent to lysine residues strongly reduced HS-mediated cell binding, further corroborating our findings. In contrast, mutation of basic surface residues located in the cleft between capsomeres outside this pocket did not significantly reduce interaction with HS or resulted in assembly-deficient proteins. Computer-simulated heparin docking suggested that all three lysine residues can form hydrogen bonds with 2-O-, 6-O-, and N-sulfate groups of a single HS molecule with a minimal saccharide domain length of eight monomer units. This prediction was experimentally confirmed in binding experiments using capsid protein, heparin molecules of defined length, and sulfate group modifications.

  5. Residues in Conserved Loops of Intramembrane Metalloprotease SpoIVFB Interact with Residues near the Cleavage Site in Pro-σK

    PubMed Central

    Zhang, Yang; Luethy, Paul M.

    2013-01-01

    Intramembrane metalloproteases (IMMPs) control critical biological processes by cleaving membrane-associated proteins within a transmembrane segment or at a site near the membrane surface. Phylogenetic analysis divides IMMPs into four groups. SpoIVFB is a group III IMMP that regulates Bacillus subtilis endospore formation by cleaving Pro-σK and releasing the active sigma factor from a membrane. To elucidate the enzyme-substrate interaction, single-cysteine versions of catalytically inactive SpoIVFB and C-terminally truncated Pro-σK(1-126) (which can be cleaved by active SpoIVFB) were coexpressed in Escherichia coli, and proximity was tested by disulfide cross-linking in vivo. As expected, the results provided evidence that catalytic residue Glu-44 of SpoIVFB is near the cleavage site in the substrate. Also near the cleavage site were two residues of SpoIVFB in predicted conserved loops; Pro-135 in a short loop and Val-70 in a longer loop. Pro-135 corresponds to Pro-399 of RseP, a group I IMMP, and Pro-399 was reported previously to interact with substrate near the cleavage site, suggesting a conserved interaction across IMMP subfamilies. Val-70 follows a newly recognized conserved motif, PXGG (X is a large hydrophobic residue), which is in a hydrophobic region predicted to be a membrane reentrant loop. Following the hydrophobic region is a negatively charged region that is conserved in IMMPs of groups I and III. At least two residues with a negatively charged side chain are required in this region for activity of SpoIVFB. The region exhibits other features in IMMPs of groups II and IV. Its possible roles, as well as that of the short loop, are discussed. New insights into IMMP-substrate interaction build toward understanding how IMMPs function and may facilitate manipulation of their activity. PMID:23995631

  6. Protein Kinase D Interacts with Neuronal Nitric Oxide Synthase and Phosphorylates the Activatory Residue Serine1412

    PubMed Central

    García-Guerra, Lucía; Pose-Utrilla, Julia; Rodríguez-Crespo, Ignacio; Iglesias, Teresa

    2014-01-01

    Neuronal Nitric Oxide Synthase (nNOS) is the biosynthetic enzyme responsible for nitric oxide (·NO) production in muscles and in the nervous system. This constitutive enzyme, unlike its endothelial and inducible counterparts, presents an N-terminal PDZ domain known to display a preference for PDZ-binding motifs bearing acidic residues at -2 position. In a previous work, we discovered that the C-terminal end of two members of protein kinase D family (PKD1 and PKD2) constitutes a PDZ-ligand. PKD1 has been shown to regulate multiple cellular processes and, when activated, becomes autophosphorylated at Ser916, a residue located at -2 position of its PDZ-binding motif. Since nNOS and PKD are spatially enriched in postsynaptic densities and dendrites, the main objective of our study was to determine whether PKD1 activation could result in a direct interaction with nNOS through their respective PDZ-ligand and PDZ domain, and to analyze the functional consequences of this interaction. Herein we demonstrate that PKD1 associates with nNOS in neurons and in transfected cells, and that kinase activation enhances PKD1-nNOS co-immunoprecipitation and subcellular colocalization. However, transfection of mammalian cells with PKD1 mutants and yeast two hybrid assays showed that the association of these two enzymes does not depend on PKD1 PDZ-ligand but its pleckstrin homology domain. Furthermore, this domain was able to pull-down nNOS from brain extracts and bind to purified nNOS, indicating that it mediates a direct PKD1-nNOS interaction. In addition, using mass spectrometry we demonstrate that PKD1 specifically phosphorylates nNOS in the activatory residue Ser1412, and that this phosphorylation increases nNOS activity and ·NO production in living cells. In conclusion, these novel findings reveal a crucial role of PKD1 in the regulation of nNOS activation and synthesis of ·NO, a mediator involved in physiological neuronal signaling or neurotoxicity under pathological conditions

  7. Comparative residue interaction analysis (CoRIA): a 3D-QSAR approach to explore the binding contributions of active site residues with ligands

    NASA Astrophysics Data System (ADS)

    Datar, Prasanna A.; Khedkar, Santosh A.; Malde, Alpeshkumar K.; Coutinho, Evans C.

    2006-06-01

    A novel approach termed comparative residue-interaction analysis (CoRIA), emphasizing the trends and principles of QSAR in a ligand-receptor environment has been developed to analyze and predict the binding affinity of enzyme inhibitors. To test this new approach, a training set of 36 COX-2 inhibitors belonging to nine families was selected. The putative binding (bioactive) conformations of inhibitors in the COX-2 active site were searched using the program DOCK. The docked configurations were further refined by a combination of Monte Carlo and simulated annealing methods with the Affinity program. The non-bonded interaction energies of the inhibitors with the individual amino acid residues in the active site were then computed. These interaction energies, plus specific terms describing the thermodynamics of ligand-enzyme binding, were correlated to the biological activity with G/PLS. The various QSAR models obtained were validated internally by cross validation and boot strapping, and externally using a test set of 13 molecules. The QSAR models developed on the CoRIA formalism were robust with good r 2, q 2 and r pred 2 values. The major highlights of the method are: adaptation of the QSAR formalism in a receptor setting to answer both the type (qualitative) and the extent (quantitative) of ligand-receptor binding, and use of descriptors that account for the complete thermodynamics of the ligand-receptor binding. The CoRIA approach can be used to identify crucial interactions of inhibitors with the enzyme at the residue level, which can be gainfully exploited in optimizing the inhibitory activity of ligands. Furthermore, it can be used with advantage to guide point mutation studies. As regards the COX-2 dataset, the CoRIA approach shows that improving Coulombic interaction with Pro528 and reducing van der Waals interaction with Tyr385 will improve the binding affinity of inhibitors.

  8. Nonsymmetric Two-Body Score Function for Protein Fold Recognition:

    NASA Astrophysics Data System (ADS)

    Heo, Muyoung; Cheon, Mookyung; Chang, Iksoo

    The usual two-body score (energy) function to recognize native folds of proteins is Miyazawa-Jernigan (MJ) pairwise-contact function. The pairwise-contact parameters between two amino acids in MJ function are symmetric in a sense that a directional order of amino acids sequence along the backbone of a protein is ignored in constructing score parameters. Here we report that we succeeded in constructing a nonsymmetric two-body score function, capturing a directional order of amino acids sequence, by a perceptron learning and a protein threading. We considered pairs of two adjacent amino acids that are separated by two consecutive peptide bonds with the backbone directionality from the N-terminus to the C-terminus of a protein. We also considered the local environmental character, such as the secondary structures and the hydrophobicity (solvation), of amino acids in protein structures. The score is a corresponding propensity for a directional alignment of these two adjacent amino acids with their local environments. The resulting score function simultaneously recognized native folds of 1006 proteins covering all representative proteins with a homology less than 30% among them. The quality of this score function was validated by a threading test of new distinct 382 proteins with a homology less than 90% among them, and it entailed a high success ratio for recognizing native folds of 364 (95.3%) proteins. It showed a good feasibility of designing protein score functions for protein fold recognition by a perceptron learning and a protein threading.

  9. CMWeb: an interactive on-line tool for analysing residue-residue contacts and contact prediction methods.

    PubMed

    Kozma, Dániel; Simon, István; Tusnády, Gábor E

    2012-07-01

    A contact map is a 2D derivative of the 3D structure of proteins, containing various residue-residue (RR) contacts within the structure. Contact maps can be used for the reconstruction of structure with high accuracy and can be predicted from the amino acid sequence. Therefore understanding the various properties of contact maps is an important step in protein structure prediction. For investigating basic properties of contact formation and contact clusters we set up an integrated system called Contact Map Web Viewer, or CMWeb for short. The server can be used to visualize contact maps, to link contacts and to show them both in 3D structures and in multiple sequence alignments and to calculate various statistics on contacts. Moreover, we have implemented five contact prediction methods in the CMWeb server to visualize the predicted and real RR contacts in one contact map. The results of other RR contact prediction methods can be uploaded as a benchmark test onto the server as well. All of these functionality is behind a web server, thus for using our application only a Java-capable web browser is needed, no further program installation is required. The CMWeb is freely accessible at http://cmweb.enzim.hu.

  10. Subnanomolar Inhibitor of Cytochrome bc1 Complex Designed via Optimizing Interaction with Conformationally Flexible Residues

    PubMed Central

    Zhao, Pei-Liang; Wang, Le; Zhu, Xiao-Lei; Huang, Xiaoqin; Zhan, Chang-Guo; Wu, Jia-Wei; Yang, Guang-Fu

    2009-01-01

    Cytochrome bc1 complex (EC 1.10.2.2, bc1), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc1 complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective π-π interactions, whereas the side chains of other hydrophobic residues showed conformational stability. Therefore, in the present study, a strategy of optimizing the π-π interaction with conformationally flexible residues was proposed to design and discover new bc1 inhibitors with a higher potency. Eight new compounds were designed and synthesized, among which compound 5c with a Ki value of 570 pM was identified as the most promising drug or fungicide candidate, significantly more potent than the commercially available bc1 inhibitors including azoxystrobin (AZ), kresoxim-methyl (KM), and pyraclostrobin (PY). To our knowledge, this is the first bc1 inhibitor discovered from structure-based design with a potency of subnanomolar Ki value. For all of the compounds synthesized and assayed, the calculated binding free energies correlated reasonably well with the binding free energies derived from the experimental Ki values with a correlation coefficient of r2 = 0.89. The further inhibitory kinetics studies revealed that compound 5c is a non-competitive inhibitor with respect to substrate cytochrome c, but is a competitive inhibitor with respect to substrate ubiquinol. Due to its subnanomolar Ki potency and slow dissociation rate constant (k−0 = 0.00358 s−1), compound 5c could be used as a specific probe for further elucidation of the mechanism of bc1 function and as a new lead compound for future drug discovery. PMID:19928849

  11. Residual quadrupole interaction in brain and its effect on quantitative sodium imaging.

    PubMed

    Stobbe, Robert W; Beaulieu, Christian

    2016-02-01

    Sodium MRI is particularly interesting given the key role that sodium ions play in cellular metabolism. To measure concentration, images must be free from contrast unrelated to sodium density. However, spin 3/2 NMR is complicated by more than rapid biexponential signal decay. Residual quadrupole interactions (described by frequency ωQ) can reduce Mxy development during RF excitation. Three experiments, each performed on the same four healthy volunteers, demonstrate that residual quadrupole interactions are of concern in quantitative sodium imaging of the brain. The first experiment shows a reliable increase in the rate of excitation 'flipping' (1%-6%), particularly in white matter with tracts running superior-inferior (i.e. parallel to B0). Increased flip-rates imply an associated signal loss and are to be expected when ωQ ~ ω1. The second experiment shows that a prescribed flip-angle decrease from 90° to 20°, with concomitant decrease in TE from 0.25 ms to 0.10 ms and no T1 weighting, results in a 14%-26% saline calibration phantom normalized signal (SN) increase in the white matter regions. The third experiment shows that this (SN) increase is primarily due to a residual quadrupole effect, with a small contribution from T2 weighting. There is an observed deviation from the spin 3/2 biexponential curve, also suggesting ωQ dephasing. Using simulation to explain the results of all three experiments, a model of brain tissue is hypothesized. It includes one pool (50%) with ωQ = 0, and another (50%) in which ωQ has a Gaussian distribution with a standard deviation of 625 Hz. Given the result of the second experiment, it is suggested that the use of reduced flip-angles with large ω1 will provide more accurate measures of sodium concentration than 'standard' methods using 90° pulses. Alternatively, further study of sodium ωQmay provide a means to explore tissue structure and organization. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Exploration of CH···π mediated stacking interactions in saccharide: aromatic residue complexes through conformational sampling.

    PubMed

    Kumari, Manju; Sunoj, Raghavan B; Balaji, Petety V

    2012-11-01

    Saccharides interact with aromatic residues mostly through CH···π mediated stacking interactions. The energetics of such interactions depends upon the mutual position-orientations (POs) of the two moieties. The POs found in the crystal structures are only a subset of the various possible ways of interaction. Hence, potential energy surfaces of saccharide-aromatic residue complexes have been explored by mixed Monte Carlo multiple minimum/low mode sampling. The saccharides considered in this study are α/β-D-glucose, β-D-galactose, α-D-mannose, and α/β-L-fucose. p-Hydroxytoluene, toluene, and 3-methylindole were used as analogs of tyrosine, phenylalanine, and tryptophan, respectively. The saccharides interact from either above or below the π-cloud of an aromatic ring but not along the edges. The POs preferred by different saccharides, both in the preferred chair and skew-boat forms, for interacting with different aromatic amino acid residue analogs have been identified. Aromatic residues can interact with the same -CH group in many POs but not so with the -OH groups. Changes in the configurations of pyranose ring carbon atoms cause remarkable changes in stacking preferences. β-D-Galactose and β-L-fructose interact only through their b- and a-faces, respectively. Saccharides use a wide variety of apolar patches for stacking against aromatic residues and these have been analyzed in detail. As many as four -CH groups can simultaneously participate in CH···π interactions, especially with 3-methylindole owing to its larger surface area.

  13. Unified analytical solutions to two-body problems with drag

    NASA Astrophysics Data System (ADS)

    Breiter, S.; Jackson, A. A.

    1998-08-01

    The two-body problem with a generalized Stokes drag is discussed. The drag force is proportional to the product of the velocity vector and the inverse square of the distance. The generalization consists of allowing two different proportionality constants for the radial and the transverse components of the force. Under the `generalized Robertson transformation', the equation of the orbit takes the form of the Lommel equation and admits solutions in terms of Bessel and Lommel functions. The exact, analytical solutions for this type of drag reveal a paradoxical effect of increasing eccentricity for all trajectories. The Poynting-Robertson drag and Poynting-Plummer-Danby problems are discussed as particular cases of the general solution.

  14. On the Manev-Type Two-Body Problem

    NASA Astrophysics Data System (ADS)

    Mioc, Vasile; Stoica, Cristina

    1997-12-01

    The two-body problem in Manev-type fields (featured by potentials of the form {A/r+B/r}(2) ; r is the distance between particles, {A} and {B} are real parameters) constitutes a good model for various concrete physical problems of astronomy, astrophysics, relativity, atomic physics, mechanics, etc. We study relative motion in such fields both quantitatively and qualitatively. An analytic solution is obtained in a closed form. A qualitative investigation is performed, representing the motion in the (1/r,dot r) phase plane, where all the solutions are conic sections (or arcs of them). A bifurcation analysis is performed case by case for the whole allowed interplay among field parameters, angular momentum and total energy. Each solution is interpreted in terms of physical motion.

  15. Nonleptonic two-body Bc-meson decays

    NASA Astrophysics Data System (ADS)

    Naimuddin, Sk.; Kar, Susmita; Priyadarsini, M.; Barik, N.; Dash, P. C.

    2012-11-01

    We study the exclusive nonleptonic two-body Bc decays within factorization approximation, in the framework of the relativistic independent quark model based on a confining potential in the scalar-vector harmonic form. The relevant weak form factors and branching ratios for different decay modes (Bc→PP,PV,VP) are predicted in reasonable agreement with other quark model predictions. We find that the dominant contribution to the Bc-meson lifetime comes from the Cabibbo-Kobayashi-Masakawa favored c¯→s¯, d¯ decay modes, and the most promising modes are found to be Bc-→B¯s0π-, Bc-→B¯s0ρ- and Bc-→B¯s⋆0π- with predicted branching ratios of 12.01, 9.96, and 8.61%, respectively, which might be easily detected at the hadron collider in the near future.

  16. Visualized kinematics code for two-body nuclear reactions

    NASA Astrophysics Data System (ADS)

    Lee, E. J.; Chae, K. Y.

    2016-05-01

    The one or few nucleon transfer reaction has been a great tool for investigating the single-particle properties of a nucleus. Both stable and exotic beams are utilized to study transfer reactions in normal and inverse kinematics, respectively. Because many energy levels of the heavy recoil from the two-body nuclear reaction can be populated by using a single beam energy, identifying each populated state, which is not often trivial owing to high level-density of the nucleus, is essential. For identification of the energy levels, a visualized kinematics code called VISKIN has been developed by utilizing the Java programming language. The development procedure, usage, and application of the VISKIN is reported.

  17. Charmless two-body antitriplet b -baryon decays

    NASA Astrophysics Data System (ADS)

    Hsiao, Y. K.; Yao, Yu; Geng, C. Q.

    2017-05-01

    We study the charmless two-body decays of b baryons (Λb , Ξb-, Ξb0 ). We find that B (Ξb-→Λ ρ-)=(2.0 8-0.51+0.69)×10-6 and B (Ξb0→Σ+M-)=(4.4 5-1.09+1.46,11.4 9-2.9+3.8,4.6 9-0.79+1.11,2.9 8-0.51+0.76)×10-6 for M-=(π-,ρ-,K-,K*-), which are compatible with B (Λb→p π-,p K-) . We also obtain that B (Λb→Λ ω )=(2.30 ±0.10 )×10-6 , B (Ξb-→Ξ-ϕ ,Ξ-ω )≃B (Ξb0→Ξ0ϕ ,Ξ0ω )=(5.35 ±0.41 ,3.65 ±0.16 )×10-6 and B (Ξb-→Ξ-η('))≃B (Ξb0→Ξ0η('))=(2.5 1-0.46+0.70,2.9 9-0.57+1.16)×10-6 . For the C P -violating asymmetries, we show that AC P(Λb→p K*-)=AC P(Ξb-→Σ0(Λ )K*-)=AC P(Ξb0→Σ+K*-)=(19.7 ±1.4 )% . Similar to the charmless two-body Λb decays, the Ξb decays are accessible to the LHCb detector.

  18. C-H…pi interactions in proteins: prevalence, pattern of occurrence, residue propensities, location, and contribution to protein stability.

    PubMed

    Kumar, Manjeet; Balaji, Petety V

    2014-02-01

    C-H…pi interactions are a class of non-covalent interactions found in different molecular systems including organic crystals, proteins and nucleic acids. High-resolution protein structures have been analyzed in the present study to delineate various aspects of C-H…pi interactions. Additionally, to determine the extent to which redundancy of a database biases the outcome, two datasets differing from each other in the level of redundancy have been analyzed. On average, only one out of six {with C-H(Aro) group} or eight {with C-H(Ali) group} residues in a protein participate as C-H group donors. Neither the frequency of occurrence in proteins nor the number of C-H groups present in it is correlated to the propensity of an amino acid to participate in C-H…pi interactions. Most of the residues that participate in C-H…pi interactions are solvent-shielded. Solvent shielded nature of most of the C-H…pi interactions and prevalence of intra- as well as inter-secondary structural element C-H…pi interactions suggest that the contribution of these interactions to the enthalpy of folded form will be significant. The separation in the primary structure between donor and acceptor residues is found to be correlated to secondary structure type. Other insights obtained from this study include the presence of networks of C-H…pi interactions spanning multiple secondary structural elements. To our knowledge this has not been reported so far. A substantial number of residues involved in C-H…pi interactions are found in catalytic and ligand binding sites suggesting their possible role in maintaining active site geometry. No significant differences of C-H…pi interactions in the two datasets are found for any of the parameters/features analyzed.

  19. A detailed study of nonperturbative solutions of two-body Dirac equations

    SciTech Connect

    Crater, H.W.; Becker, R.L.; Wong, C.Y.; Van Alstine, P.

    1992-12-01

    In quark model calculations of the meson spectrums fully covariant two-body Dirac equations dictated by Dirac's relativistic constraint mechanics gave a good fit to the entire meson mass spectrum for light quark mesons as well as heavy quark mesons with constituent world scalar and vector potentials depending on just one or two parameters. In this paper, we investigate the properties of these equations that made them work so well by solving them numerically for quantum electrodynamics (QED) and related field theories. The constraint formalism generates a relativistic quantum mechanics defined by two coupled Dirac equations on a sixteen component wave function which contain Lorentz covariant constituent potentials that are initially undetermined. An exact Pauli reduction leads to a second order relativistic Schroedinger-like equation for a reduced eight component wave function determined by an effective interaction -- the quasipotential. We first determine perturbatively to lowest order the relativistic quasipotential for the Schroedinger-like equation by comparing that form with one derived from the Bethe-Salpeter equation. Insertion of this perturbative information into the minimal interaction structures of the two-body Dirac equations then completely determines their interaction structures. Then we give a procedure for constructing the full sixteen component solution to our coupled first-order Dirac equations from a solution of the second order equation for the reduced wave function. Next, we show that a perturbative treatment of these equations yields the standard spectral results for QED and related interactions.

  20. [Interactions between natural vegetation succession and waste residue in lead-zinc tailings deposited sites].

    PubMed

    Liu, Hong-yan; Xing, Dan; Xlao, Jiu-jun; Liu, Fang

    2010-12-01

    Natural vegetation succession process and related mechanism is one of the important research contents in ecological restoration of abandoned mining land. Taking 4 lead-zinc tailings deposited sites with the recovery time being about 10 years, 20 years, 30 year, and over 40 years under similar site conditions in northwest Guizhou Provinnce as study areas, this paper studied the interactions between the natural vegetation succession and the physicochemical properties of waste residue. The results showed that with the increasing dumping time of the waste residue, the nutritional conditions of base material improved significantly, the total N, P, and K contents and the pH value increased, while the EC, bulk density, and especially, available lead and cadmium contents decreased. Meanwhile, the plant community species richness (S), diversity index (H), and evenness (J) increased correspondingly with increasing recovery time. The composition of plant communities was dominated by perennial herbaceous. In the first 20 years of recovery, the vegetation succession process was very slow, but after 30- and 40-year recovery, the vegetation coverage reached 53% and 87%, respectively. Canonical correlation analysis showed that there were significant correlations between base material properties and species diversity, and the canonical variables were the total N, P, and K contents of base material. The species diversity index was significantly negatively correlated with the available Pb and Cd contents of base material. The natural vegetation succession process in the study areas accelerated after 30 years of recovery, and the limiting factors of vegetation recovery were the nutrient deficiency and the high availability of Pb and Cd in base material.

  1. Probing Interactions between Lysine Residues in Histone Tails and Nucleosomal DNA via Product and Kinetic Analysis

    PubMed Central

    2015-01-01

    The histone proteins in nucleosome core particles are known to catalyze DNA cleavage at abasic and oxidized abasic sites, which are produced by antitumor antibiotics and as a consequence of other modalities of DNA damage. The lysine rich histone tails whose post-translational modifications regulate genetic expression in cells are mainly responsible for this chemistry. Cleavage at a C4′-oxidized abasic site (C4-AP) concomitantly results in modification of lysine residues in histone tails. Using LC-MS/MS, we demonstrate here that that Lys8, -12, -16, and -20 of histone H4 were modified when C4-AP was incorporated at a hot spot (superhelical location 1.5) for DNA damage within a nucleosome core particle. A new DNA–protein cross-linking method that provides a more quantitative analysis of individual amino acid reactivity is also described. DNA–protein cross-links were produced by an irreversible reaction between a nucleic acid electrophile that was produced following oxidatively induced rearrangement of a phenyl selenide derivative of thymidine (3) and nucleophilic residues within proteins. In addition to providing high yields of DNA–protein cross-links, kinetic analysis of the cross-linking reaction yielded rate constants that enabled ranking the contributions by individual or groups of amino acids. Cross-linking from 3 at superhelical location 1.5 revealed the following order of reactivity for the nucleophilic amino acids in the histone H4 tail: His18 > Lys16 > Lys20 ≈ Lys8, Lys12 > Lys5. Cross-linking via 3 will be generally useful for investigating DNA–protein interactions. PMID:25475712

  2. Fibrinogen residue γAla341 is necessary for calcium binding and 'A-a' interactions.

    PubMed

    Park, Rojin; Ping, Lifang; Song, Jaewoo; Hong, Sung-Yu; Choi, Tae-Youn; Choi, Jong-Rak; Gorkun, Oleg V; Lord, Susan T

    2012-05-01

    The fibrinogen γ-module has several important sites relating to fibrinogen function, which include the high affinity calcium binding site, hole 'a' that binds with knob 'A', and the D:D interface. Residue γAla341, which is located in the vicinity of these sites, is altered in three variant fibrinogens: fibrinogen Seoul (γAla341Asp), Tolaga Bay (γAla341Val), and Lyon III (γAla341Thr). In order to investigate the impaired polymerisation of fibrinogens γAla341Asp and γAla341Val to understand the role of γAla341 in fibrin polymerisation and fibrinogen synthesis, we have expressed γAla341Asp and γAla341Val in Chinese hamster ovary (CHO) cells, purified these fibrinogens from the culture media and performed biochemical tests to elucidate their function. Expression in CHO cells was similar for these variants. For both variants the kinetics of thrombin-catalysed FpA release was not different from normal fibrinogen, while FpB release was slower than that of normal. Thrombin-catalysed polymerisation of both variants was dependent on the calcium concentration. At physiologic calcium (1 mM) the variants showed impaired polymerisation with a longer lag period and a slower Vmax than normal fibrinogen. Scanning electron micrographs showed the clots were less organised than normal, having thicker and more twisted fibers, and larger pores. Analysis by SDS-PAGE showed that factor XIIIa-catalysed γ and α chain cross-linking was delayed, and plasmin-catalysed lysis was not reduced by the presence of 5 mM calcium or 5 mM GPRP (Gly-Pro-Arg-Pro). Our data indicate that fibrinogen residue γAla341 is important for the proper conformation of the γ-module, maintaining calcium-binding site and 'A-a' interactions.

  3. Two-body density matrix of a normal Fermi fluid

    NASA Astrophysics Data System (ADS)

    Ristig, M. L.; Clark, J. W.

    1990-05-01

    The microscopic study of the two-body density matrix ρ2(r1,r2,r'1,r'2) initiated for uniform Bose fluids in an earlier paper is continued for the Fermi case. We present formal results on the structure of the generalized momentum distribution n(p,q)=Σk⁁<Ψ\\|a†k⁁+qa†p⁁-qap⁁ak⁁\\|Ψ>, and its Fourier inverse ρ2(r1,r2,r'1,r2)≡ρ2(r1,r2,r'1), based on a variational ground-state wave function of Jastrow-Slater form. The structural relations are inferred from the cluster expansions of these objects, from the asymptotic condition relating ρ2(r1,r2,r'1) to the particle density and the one-body density matrix ρ1(r1,r'1), and from formal diagrammatic connections with the Bose problem. The two-body density-matrix elements ρ2(r1,r2,r'1) are thereby expressed in closed form in terms of certain sums of irreducible cluster diagrams. Some of these diagram sums are familiar from the analogous theory of the one-body density matrix; all can be evaluated quantitatively by solving a set of Fermi-hypernetted-chain (FHNC) equations. Upon invoking the sequential relation between ρ2(r1,r2,r'1) and ρ1(r1,r'1), the corresponding result for the generalized momentum distribution n(p,q) effects a resolution into contributions from various scattering processes occurring in the many-body medium, specified by form factors that are susceptible to FHNC evaluation. This decomposition is comparable to that derived earlier for the Bose-fluid ground state but is complicated by contributions from exchange scattering and by a dynamically dressed Pauli kinematic correction. Silver has proposed a simple expression for the generalized momentum distribution n(p,q), a function which plays an essential role in his theory of final-state effects in deep-inelastic neutron scattering from the helium liquids. Based on the present microscopic treatment, the quality of Silver's estimate is assessed for the case of normal liquid He3, by evaluating the necessary distribution

  4. Material loss in two-body collisions during planet formation

    NASA Astrophysics Data System (ADS)

    Werner, J.; Schäfer, C.; Maindl, T. I.; Burger, C.; Speith, R.

    2016-02-01

    During the formation process of a terrestrial planet, a planetary embryo does not only accrete smaller dust particles but also suffers collisions with larger planetesimals. When simulating these collisions, most N-body codes treat them as perfect merging events, i.e. the resulting body's mass is the sum of the previous ones. In our work, we aim to determine whether this assumption is a justified simplification, specifically focusing on bodies containing volatile elements, such as water. To analyze this, we have developed a new Smooth Particle Hydrodynamics (SPH) code that includes elasto-plastic dynamics, a damage model for brittle materials and self gravity. It makes use of the Compute Unified Device Architecture (CUDA) and runs on modern GPU architectures which allows for higher resolution in less calculation time. This enables us to take a precise look at two-body collisions and determine the amount of both transferred and ejected mass according to specific parameters such as mass ratio of impactor and target, porosity, impact velocity, impact angle and water distribution.

  5. Interactions between allelochemicals and the microbial community affect weed suppression following cover crop residue incorporation into soil

    USDA-ARS?s Scientific Manuscript database

    The objective of this study is to understand how soil microorganisms interact with cover crop-derived allelochemicals to suppress weed germination and growth following cover crop residue incorporation. We conducted a time series experiment by crossing sterilized and non-sterilized soil with four dif...

  6. Investigation of electrostatic interactions in two-stranded coiled-coils through residue shuffling.

    PubMed

    Yu, Y; Monera, O D; Hodges, R S; Privalov, P L

    1996-04-16

    The effects of electrostatic interactions on the stability of coiled-coils were investigated using the strategy of shuffling the sequence without changing the overall content of amino acid residues in the peptides. Shuffling the sequence provides peptides with thermodynamically similar unfolded states. Therefore, the unfolded state can be used as a universal reference state in comparing the thermodynamic properties of the folded coiled-coil structure of the peptides, while varying the configuration of ionized groups, that is, changing the types and number of potential electrostatic interactions. The relative stabilities of these states were determined by monitoring the temperature-induced folding/unfolding of the peptides in solutions with different pH and ionic strength by circular dichroism spectroscopy and scanning microcalorimetry. It was found that, in solutions with low ionic strength, ionic pairs contribute significantly to the stability of the coiled-coil conformation. The stability increases with an increase in the number of ionized groups in the peptide upon changing pH from acidic to neutral. In contrast, in the solutions with high ionic strength, the coiled-coil becomes less stable at neutral pH than at acidic pH. Most surprisingly, the increase in Gibbs energy of stabilization of the coiled-coil state with increasing pH at low ionic strength proceeds with a decrease in the enthalpy and entropy of unfolding. This observation can be explained only by hydration of ionized groups upon unfolding of coiled-coils which is associated with significant negative enthalpy and entropy effects.

  7. Residue Coulomb Interaction Among Isobars and Its Influence in Symmetry Energy of Neutron-Rich Fragment

    NASA Astrophysics Data System (ADS)

    Ma, Chun-Wang; Wang, Shan-Shan; Zhang, Yan-Li; Zhao, Yi-Long; Wei, Hui-Ling

    2015-09-01

    The residue Coulomb interaction (RCI), which affects the result of symmetry-energy coefficient of neutron-rich nucleus in isobaric yield ratio (IYR) method, is difficult to be determined. Four RCI approximations are investigated: (i) The M1-RCI adopting the ac/T (the ratio of Coulomb energy coefficient to temperature) determined from the IYR of mirror-nucleus fragments; (ii) The M2-RCI by fitting the difference between IYRs; (iii) The M3-RCI adopting the standard Coulomb energy at a temperature T = 2 MeV; and (iv) Neglecting the RCI among isobars. The M1-, M2- and M3-RCI are no larger than 0.4. In particular, the M2-RCI is very close to zero. The effects of RCI in asym/T of fragment are also studied. The M1- and M4-asym/T are found to be the lower and upper limitations of asym/T, respectively. The M2-asym/T overlaps the M4-asym/T, which indicates that the M2-RCI is negligible in the IYR method, and the RCI among the three isobars can be neglected. The relative consistent low values of M3-asym/T (7.5 ± 2.5) are found in very neutron-rich isobars. Supported by the Program for Science & Technology Innovation Talents in Universities of Henan Province (13HASTIT046), and Young Teacher Project in Henan Normal University (HNU), China

  8. Interaction between carbohydrate residues of alpha1-acid glycoprotein (orosomucoid) and saturating concentrations of Calcofluor White. A fluorescence study.

    PubMed

    Albani, J R; Sillen, A; Plancke, Y D; Coddeville, B; Engelborghs, Y

    2000-07-24

    Calcofluor White is a fluorescent probe that interacts with polysaccharides and is commonly used in clinical studies. Interaction between Calcofluor White and carbohydrate residues of alpha1-acid glycoprotein (orosomucoid) was previously followed by fluorescence titration of the Trp residues of the protein. A stoichiometry of one Calcofluor for one protein has been found [J.R. Albani and Y.D. Plancke, Carbohydr. Res., 318 (1999) 193-200]. Alpha1-acid glycoprotein contains 40% carbohydrate by weight and has up to 16 sialic acid residues. Since binding of Calcofluor to alpha1-acid glycoprotein occurs mainly on the carbohydrate residues, we studied in the present work the interaction between Calcofluor and the protein by following the fluorescence change of the fluorophore. In order to establish the role of the sialic acid residues in the interaction, the experiments were performed with the sialylated and asialylated protein. Interaction of Calcofluor with sialylated alpha1-acid glycoprotein induces a red shift of the emission maximum of the fluorophore from 438 to 450 nm at saturation (one Calcofluor for one sialic acid) and an increase in the fluorescence intensity. At saturation the fluorescence intensity increase levels off. Binding of Calcofluor to asialylated acid glycoprotein does not change the position of the emission maximum of the fluorophore and induces a decrease in its fluorescence intensity. Saturation occurs when 10 molecules of Calcofluor are bound to 1 mol of alpha1-acid glycoprotein. Since the protein contains five heteropolysaccharide groups, we have 2 mol of Calcofluor for each group. Addition of free sialic acid to Calcofluor induces a continuous decrease in the fluorescence intensity of the fluorophore but does not change the position of the emission maximum. Our results confirm the presence of a defined spatial conformation of the sialic acid residues, a conformation that disappears when they are free in solution. Dynamics studies on Calcofluor

  9. NMR analysis of cross strand aromatic interactions in an 8 residue hairpin and a 14 residue three stranded β-sheet peptide.

    PubMed

    Sonti, Rajesh; Rai, Rajkishor; Ragothama, Srinivasarao; Balaram, Padmanabhan

    2012-12-13

    Cross strand aromatic interactions between a facing pair of phenylalanine residues in antiparallel β-sheet structures have been probed using two structurally defined model peptides. The octapeptide Boc-LFV(D)P(L)PLFV-OMe (peptide 1) favors the β-hairpin conformation nucleated by the type II' β-turn formed by the (D)Pro-(L)Pro segment, placing Phe2 and Phe7 side chains in proximity. Two centrally positioned (D)Pro-(L)Pro segments facilitate the three stranded β-sheet formation in the 14 residue peptide Boc-LFV(D)P(L)PLFVA(D)P(L)PLFV-OMe (peptide 2) in which the Phe2/Phe7 orientations are similar to that in the octapeptide. The anticipated folded conformations of peptides 1 and 2 are established by the delineation of intramolecularly hydrogen bonded NH groups and by the observation of specific cross strand NOEs. The observation of ring current shifted aromatic protons is a diagnostic of close approach of the Phe2 and Phe7 side chains. Specific assignment of aromatic proton resonances using HSQC and HSQC-TOCSY methods allow an analysis of interproton NOEs between the spatially proximate aromatic rings. This approach facilitates specific assignments in systems containing multiple aromatic rings in spectra at natural abundance. Evidence is presented for a dynamic process which invokes a correlated conformational change about the C(α)-C(β)(χ(1)) bond for the pair of interacting Phe residues. NMR results suggest that aromatic ring orientations observed in crystals are maintained in solution. Anomalous temperature dependence of ring current induced proton chemical shifts suggests that solvophobic effects may facilitate aromatic ring clustering in apolar solvents.

  10. On the Mass Difference Between pi and rho Using a Relativistic Two-Body Model

    SciTech Connect

    Wong, Cheuk-Yin; Kim, Byeong-Noh; Crater, H. W.; Yoon, Jin-Hee

    2012-01-01

    The big mass difference between the pion(pi) and rho meson(rho) possibly originated from the spin-dependent nature of the interactions in the two states since these two states are similar except for spin. Both pi and rho are quark-antiquark systems which can be treated using the two-body Dirac equations (TBDE) of constraint dynamics. This relativistic approach for the two-body system has the advantage over the non-relativistic treatment in the sense that the spin-dependent nature is automatically coming out from the formalism. We employed Dirac's relativistic constraint dynamics to describe quark-antiquark systems. Within this formalism, the 16-component Dirac equation is reduced to the 4-component 2nd-order differential equation and the radial part of this equation is simply a Schroedinger-type equation with various terms calculated from the basic radial potential. We used a modified Richardson potential for quark-antiquark systems which satisfies the conditions of confinement and asymptotic freedom. We obtained the wave functions for these two mesons which are not singular at short distances. We also found that the cancellation between the Darwin and spin-spin interaction terms occurs in the pi mass but not in the rho mass, and this is the main source of the big difference in the two meson masses.

  11. Increasing protein stability by polar surface residues : domain-wide consequences of interactions within a loop.

    SciTech Connect

    Pokkuluri, P. R.; Raffen, R.; Dieckman, L.; Boogaard, C.; Stevens, F. J.; Schiffer, M.; Biosciences Division; C. Boogaard

    2002-01-01

    We have examined the influence of surface hydrogen bonds on the stability of proteins by studying the effects of mutations of human immunoglobulin light chain variable domain (V(L)). In addition to the variants Y27dD, N28F, and T94H of protein kappa IV Len that were previously described, we characterized mutants M4L, L27cN, L27cQ, and K39T, double mutant M4L/Y27dD, and triple mutant M4L/Y27dD/T94H. The triple mutant had an enhanced thermodynamic stability of 4.2 kcal/mol. We determined the structure of the triple mutant by x-ray diffraction and correlated the changes in stability due to the mutations with changes in the three-dimensional structure. Y27dD mutant had increased stability of Len by 2.7 kcal/mol, a large value for a single mutation. Asp27d present in CDR1 formed hydrogen bonds with the side-chain and main-chain atoms within the loop. In the case of the K39T mutant, which reduces stability by 2 kcal/mol, Lys39 in addition to forming a hydrogen bond with a carbonyl oxygen of a neighboring loop may also favorably influence the surface electrostatics of the molecule. We showed that hydrogen bonds between residues in surface loops can add to the overall stability of the V(L) domains. The contribution to stability is further increased if the surface residue makes more than one hydrogen bond or if it forms a hydrogen bond between neighboring turns or loops separated from each other in the amino acid sequence. Based on our experiments we suggest that stabilization of proteins might be systematically accomplished by introducing additional hydrogen bonds on the surface. These substitutions are more straightforward to predict than core-packing interactions and can be selected to avoid affecting the protein's function.

  12. Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I alpha-helical residues.

    PubMed

    Hornell, T M; Solheim, J C; Myers, N B; Gillanders, W E; Balendiran, G K; Hansen, T H; Connolly, J M

    1999-09-15

    The molecular basis for the difference in the strength of T cell responses to self vs alloantigens is unknown, but may reflect how T cells are selected in the thymus. Because T cells with a high affinity for foreign as opposed to self MHC molecules are able to mature, it has been proposed that alloreactive T cells may be more strongly dependent upon interaction with MHC residues than are self-restricted T cells. This study was undertaken to rigorously address this hypothesis. Whereas other studies have compared self vs alloantigen recognition of different MHC alleles by a single T cell clone, we have compared self vs alloantigen recognition of a single MHC allele, H-2Ld, by a large panel of self-restricted and alloreactive T cell clones. Target cells expressing Ld molecules mutated at several different potential TCR contact residues were analyzed to determine which residues are important for recognition by self-restricted vs alloreactive T cells. We unequivocally demonstrate that self-restricted and alloreactive T cells do not differ, but rather are comparably dependent on interaction with MHC residues. Importantly, both self-restricted and alloreactive T cells are dependent upon the same MHC residues as primary contacts and, in addition, share a common recognition pattern of Ld. Furthermore, our analysis enables us to provide a model for allotype-specific T cell recognition of Ld vs Kb class I molecules.

  13. Two-body wear of occlusal splint materials.

    PubMed

    Kurt, H; Erdelt, K-J; Cilingir, A; Mumcu, E; Sülün, T; Tuncer, N; Gernet, W; Beuer, F

    2012-08-01

    This study investigates the wear resistance of four different types of occlusal splint materials based on two-body wear simulations under wet and dry conditions. Twenty specimens of each splint material (Dentalon Plus, Orthoplast, Biocryl C, and Eclipse), each with a diameter of 16 mm and a thickness of 3 mm, were tested, half under wet and half under dry conditions. Each wear test was performed using a device called chewing simulator CS-4 (n=10; test load: 50 N; number of cycles: 10000, 20000, and 30000; continuous rinsing with 30°C water for wet conditions); the antagonists were simulated using steel balls. Wear was determined using a 3D laser scanner and a surface analysis program. To detect significant statistical differences, wear data after 10000; 20000; and 30000 cycles were compared using the Kruskal-Wallis test and the Mann-Whitney U-test. The level of significance was set at 5%. Significant differences were found between the groups of different materials tested under wet conditions (P<0.05), whereas no differences between them were found under dry conditions (P>0.05). No significant difference was found between the wet and dry conditions for all materials and cycles (P>0.05). For groups of different materials tested under wet conditions, the degree of volume loss generated in the Chewing Simulator CS-4 was found to differ significantly for different numbers of cycles. The presence of water had no effect on the volume loss in the different material groups that were tested.

  14. Interaction between soil mineralogy and the application of crop residues on aggregate stability and hydraulic conductivity of the soil

    NASA Astrophysics Data System (ADS)

    Lado, M.; Kiptoon, R.; Bar-Tal, A.; Wakindiki, I. I. C.; Ben-Hur, M.

    2012-04-01

    One of the main goals of modern agriculture is to achieve sustainability by maintaining crop productivity while avoiding soil degradation. Intensive cultivation could lead to a reduction in soil organic matter that could affect the structure stability and hydraulic conductivity of the soil. Moreover, crops extract nutrients from the soil that are taken away from the field when harvested, and as a consequence, the addition of fertilizers to the soil is necessary to maintain crop productivity. One way to deal with these problems is to incorporate crop residues into the soil after harvest. Crop residues are a source of organic matter that could improve soil physical properties, such as aggregate stability and soil hydraulic conductivity. However, this effect could vary according to other soil properties, such as clay content, clay mineralogy, and the presence of other cementing materials in the soil (mainly carbonates and aluminum and iron oxides). In the present work, the interaction between the addition of chickpea crop residues to the soil and clay mineralogy on aggregate stability and saturated hydraulic conductivity were studied. Chickpea plant residues were added at a rate of 0.5% (w/w) to smectitic, kaolinitic, illitic and non-phyllosilicate soils from different regions. The soils without (control) and with chickpea residues were incubated for 0, 3, 7 and 30 days, and the saturated hydraulic conductivity of the soils was measured in columns after each incubation time. The response of hydraulic conductivity to the addition of residues and incubation time was different in the soils with various mineralogies, although in general, the addition of chickpea residues increased the saturated hydraulic conductivity as compared with the control soils. This positive effect of crop residues on hydraulic conductivity was mainly a result of improved aggregate stability and resistance to slaking during wetting.

  15. One plus two-body random matrix ensembles with parity: Density of states and parity ratios

    SciTech Connect

    Vyas, Manan; Srivastava, P. C.; Kota, V. K. B.

    2011-06-15

    One plus two-body embedded Gaussian orthogonal ensemble of random matrices with parity [EGOE(1+2)-{pi}] generated by a random two-body interaction (modeled by GOE in two-particle spaces) in the presence of a mean field for spinless identical fermion systems is defined, generalizing the two-body ensemble with parity analyzed by Papenbrock and Weidenmueller [Phys. Rev. C 78, 054305 (2008)], in terms of two mixing parameters and a gap between the positive ({pi}=+) and negative ({pi}=-) parity single-particle (sp) states. Numerical calculations are used to demonstrate, using realistic values of the mixing parameters appropriate for some nuclei, that the EGOE(1+2)-{pi} ensemble generates Gaussian form (with corrections) for fixed parity eigenvalue densities (i.e., state densities). The random matrix model also generates many features in parity ratios of state densities that are similar to those predicted by a method based on the Fermi-gas model for nuclei. We have also obtained, by applying the formulation due to Chang et al. [Ann. Phys. (NY) 66, 137 (1971)], a simple formula for the spectral variances defined over fixed-(m{sub 1},m{sub 2}) spaces, where m{sub 1} is the number of fermions in the positive parity sp states and m{sub 2} is the number of fermions in the negative parity sp states. Similarly, using the binary correlation approximation, in the dilute limit, we have derived expressions for the lowest two-shape parameters. The smoothed densities generated by the sum of fixed-(m{sub 1},m{sub 2}) Gaussians with lowest two-shape corrections describe the numerical results in many situations. The model also generates preponderance of positive parity ground states for small values of the mixing parameters, and this is a feature seen in nuclear shell-model results.

  16. Ionic interaction of positive amino acid residues of fungal hydrophobin RolA with acidic amino acid residues of cutinase CutL1.

    PubMed

    Takahashi, Toru; Tanaka, Takumi; Tsushima, Yusei; Muragaki, Kimihide; Uehara, Kenji; Takeuchi, Shunsuke; Maeda, Hiroshi; Yamagata, Youhei; Nakayama, Mayumi; Yoshimi, Akira; Abe, Keietsu

    2015-04-01

    Hydrophobins are amphipathic proteins secreted by filamentous fungi. When the industrial fungus Aspergillus oryzae is grown in a liquid medium containing the polyester polybutylene succinate co-adipate (PBSA), it produces RolA, a hydrophobin, and CutL1, a PBSA-degrading cutinase. Secreted RolA attaches to the surface of the PBSA particles and recruits CutL1, which then condenses on the particles and stimulates the hydrolysis of PBSA. Here, we identified amino acid residues that are required for the RolA-CutL1 interaction by using site-directed mutagenesis. We quantitatively analyzed kinetic profiles of the interactions between RolA variants and CutL1 variants by using a quartz crystal microbalance (QCM). The QCM analyses revealed that Asp142, Asp171 and Glu31, located on the hydrophilic molecular surface of CutL1, and His32 and Lys34, located in the N-terminus of RolA, play crucial roles in the RolA-CutL1 interaction via ionic interactions. RolA immobilized on a QCM electrode strongly interacted with CutL1 (K(D)  = 6.5 nM); however, RolA with CutL1 variants, or RolA variants with CutL1, showed markedly larger KD values, particularly in the interaction between the double variant RolA-H32S/K34S and the triple variant CutL1-E31S/D142S/D171S (K(D)  = 78.0 nM). We discuss a molecular prototype model of hydrophobin-based enzyme recruitment at the solid-water interface. © 2015 John Wiley & Sons Ltd.

  17. Folding domains and intramolecular ionic interactions of lysine residues in glyceraldehyde 3-phosphate dehydrogenase.

    PubMed Central

    Lambert, J M; Perham, R N

    1977-01-01

    the view that the ion-pair involving lysine-306 and aspartic acid-241 will be a common structural feature in glyceraldehyde-3-phosphate dehydrogenases. The B. stearothermophilus enzyme was fully active after modification. 5. No differences could be detected between the enzymes from ox muscle and ox liver, in accord with other evidence that points to the identify of these enzymes. 6. The pattern of slowly reacting amino groups in the enzyme from B. stearothermophilus, although similar to that of the mammalian enzymes, indicated one or two additional intramolecular ionic interactions of lysine residues that might contribute to the thermal stability of this enzyme. Images PLATE 1 PLATE 2 PMID:851424

  18. Critical regions and residues for self-interaction of grapevine leafroll-associated virus 2 protein p24.

    PubMed

    Liu, Qing; Guo, Ran; Li, Mingjun; Feng, Ming; Wang, Xianyou; Wang, Qi; Cheng, Yuqin

    2016-07-15

    The 24-kDa protein (p24) encoded by grapevine leafroll-associated virus 2 (GLRaV-2) is an RNA-silencing suppressor. In this work, a yeast two-hybrid system (YTHS) and bimolecular fluorescence complementation analyses showed that GLRaV-2 p24 can interact with itself, and that this interaction occurs in the cytoplasm of Nicotiana benthamiana cells. To identify the functional region(s) and crucial amino acid residues required for p24 self-interaction, various truncated and substitution mutants were generated. YTHS assay showed that in both homologous pairing and pairing with the wild-type p24, the functional regions mapped to aa 10-180 or 1-170 which contain, respectively, all seven α-helices or the first six α-helices and the N-terminal end (aa 1-9) of the protein. When only the full-length p24 was an interaction partner, the functional region of aa 1-170 could be further mapped to aa 1-140 which contains four α-helices plus most of the fifth α-helix. Further analysis with substitution mutants demonstrated that hydrophobic residues I35/F38/V85/V89/W149 and V162/L169/L170, which may, respectively, mediate the inter-domain interaction of the same p24 monomer and the tail-to-tail association between two p24 counterparts, are crucial for homotypic p24-p24 interaction. In addition, substitution of two basic residues-R2 or R86-of p24, which may play important functional roles in RNA binding, did not seem to affect self-interaction of the mutants in yeast but had obvious effects in plant cells. Taken together, our results demonstrate the functional regions and crucial amino acids for p24 self-interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Experimental Investigations on Fatigue Damage and Residual Properties of Interacting Notched Woven E-Glass/Epoxy Composite

    NASA Astrophysics Data System (ADS)

    Bhaskara Rao, Pathakokila; Rama Krishna, Avasarala; Ramji, Koona; Satya Devi, Ambadipudi

    2015-10-01

    The interacting notched laminates of plain weave E-glass fiber reinforced with epoxy were fatigued at predetermined frequency in tension-tension to investigate the fatigue damage and residual properties. The results from stress-life curves summarize that damage growing around the notches due to stress concentration is the underlying cause for the variation in fatigue strengths among the geometrically different specimens considered. The residual strength and modulus decay with respect to cycle number at 50 % of the ultimate tensile strength were investigated. It is evident from the experimental data that the residual strength decreases with cycle number and increases due to redistribution of stress around the notches. The detailed study of the damage development under cyclic loads also explains the causes of modulus reduction for all the laminate geometries.

  20. Analysis of conformational motions and related key residue interactions responsible for a specific function of proteins with elastic network model.

    PubMed

    Su, Ji Guo; Han, Xiao Ming; Zhang, Xiao; Hou, Yan Xue; Zhu, Jian Zhuo; Wu, Yi Dong

    2016-01-01

    Protein collective motions play a critical role in many biochemical processes. How to predict the functional motions and the related key residue interactions in proteins is important for our understanding in the mechanism of the biochemical processes. Normal mode analysis (NMA) of the elastic network model (ENM) is one of the effective approaches to investigate the structure-encoded motions in proteins. However, the motion modes revealed by the conventional NMA approach do not necessarily correspond to a specific function of protein. In the present work, a new analysis method was proposed to identify the motion modes responsible for a specific function of proteins and then predict the key residue interactions involved in the functional motions by using a perturbation approach. In our method, an internal coordinate that accounts for the specific function was introduced, and the Cartesian coordinate space was transformed into the internal/Cartesian space by using linear approximation, where the introduced internal coordinate serves as one of the axes of the coordinate space. NMA of ENM in this internal/Cartesian space was performed and the function-relevant motion modes were identified according to their contributions to the specific function of proteins. Then the key residue interactions important for the functional motions of the protein were predicted as the interactions whose perturbation largely influences the fluctuation along the internal coordinate. Using our proposed methods, the maltose transporter (MalFGK2) from E. Coli was studied. The functional motions and the key residue interactions that are related to the channel-gating function of this protein were successfully identified.

  1. Ultralow field magnetization reversal of two-body Stoner particles system

    NASA Astrophysics Data System (ADS)

    Li, Fei; Lu, Xiaofeng; Tang, Rujun; Sun, Z. Z.

    Magnetic mechanism of nanoparticles has attracted explosive attention in the development of modern information industry. On the base of Landau-Lifshitz-Gilbert equation, we studied the magnetization reversal in a system of two Stoner particles with uniaxial anisotropies and static magnetic interaction. Using micromagnetic simulation, two typical geometrical configurations of perpendicular(PERP) and parallel(PARA) configuration where the diameter of each particle is 20nm are considered. We found that when the separation between two particles has 23nm in PERP configuration ultralow switching field strength, 17mT can be realized, which satisfies the zero-field condition in our previous works[J. Appl. Phys. 109, 104303(2011)] according to the chosen parameters of cobalt material. For other separation values the switching field are multiple of lowest field. However, in PARA configuration the switching field changes with the separation faintly. This two-body system considered in our work might be implement as a composite information bit and our results offer further possibilities for its applications in information storage and/or fast magnetic response. Ultralow field magnetization reversal of two-body Stoner particles system.

  2. Global solutions to the electrodynamic two-body problem on a straight line

    NASA Astrophysics Data System (ADS)

    Bauer, G.; Deckert, D.-A.; Dürr, D.; Hinrichs, G.

    2017-06-01

    The classical electrodynamic two-body problem has been a long standing open problem in mathematics. For motion constrained to the straight line, the interaction is similar to that of the two-body problem of classical gravitation. The additional complication is the presence of unbounded state-dependent delays in the Coulomb forces due to the finiteness of the speed of light. This circumstance renders the notion of local solutions meaningless, and therefore, straightforward ODE techniques cannot be applied. Here, we study the time-symmetric case, i.e., the Fokker-Schwarzschild-Tetrode (FST) equations, comprising both advanced and retarded delays. We extend the technique developed in Deckert and Hinrichs (J Differ Equ 260:6900-6929, 2016), where existence of FST solutions was proven on the half line, to ensure global existence—a result that had been obtained by Bauer (Ein Existenzsatz für die Wheeler-Feynman-Elektrodynamik, Herbert Utz Verlag, München, 1997). Due to the novel technique, the presented proof is shorter and more transparent but also relies on the idea to employ asymptotic data to characterize solutions.

  3. Braids in a two-body micro swimming

    NASA Astrophysics Data System (ADS)

    Mirzakhanloo, Mehdi; Jalali, Mir Abbas; Alam, M.-Reza

    2016-11-01

    Here we show that microswimmers' trajectories may get entangled as a result of their mutual hydrodynamic interactions, resulting in a group behavior that is significantly different from individual swimmers' trajectories. Specifically, we consider a two-swimmer motion of "Quadroar", a newly proposed swimmer consists of two axles of rotating disks connected through a linear reciprocating actuator. In the absence of hydrodynamic interaction, each microswimmer moves along a straight path. When hydrodynamic interaction is introduced, the two swimmers move along tightly woven trajectories whose properties depend on the swimmers' initial conditions. We also show that if swimmers are sent toward each other they may reach an equilibrium at which while they are swimming (i.e. spending energy) no net motion is achieved. We further discuss that since the streamlines of the flow induced by the Quadroar closely resemble the oscillatory flow field of the green alga Chlamydomonas reinhardtii, our findings can thus be utilized to understand the interactions of microorganisms with each other.

  4. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface

    PubMed Central

    Ansari, Shabbir A.; Pendurthi, Usha R.; Sen, Prosenjit; Rao, L. Vijaya Mohan

    2016-01-01

    Exposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF) decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF. PMID:27348126

  5. Identification of TyeA residues required to interact with YopN and to regulate Yop secretion.

    PubMed

    Joseph, Sabrina S; Plano, Gregory V

    2007-01-01

    The secretion of Yops via the Yersinia type III secretion system (T3SS) is controlled, in part, by a cytoplasmic YopN/TyeA complex. This complex is required to prevent Yop secretion in the presence of extracellular calcium and prior to contact between the bacterium and a eukaryotic cell. In this study we utilized site-directed mutagenesis to analyze the role of specific TyeA regions and residues in the regulation of Yop secretion. We identified two spatially distinct, surface-exposed regions of the TyeA molecule that were required to regulate Yop secretion. One region, identified by residues M51, F55 and P56, was required for TyeA to interact with YopN. A second region, identified by residues R19, W20 and D25 was not involved in the interaction of TyeA with YopN, but may be required for the YopN/TyeA complex to interact with the T3S apparatus in a manner that blocks Yop secretion.

  6. Effective Field Theory Description of Two-Body Resonance States

    NASA Astrophysics Data System (ADS)

    Balalhabashi, Jaber

    2017-01-01

    The quantum-mechanical scattering of two particles around a resonance state appears in many areas of physics, for example in cold atoms near narrow, low-lying Feshbach resonances. We construct) an EFT that describes such scattering with contact, derivative interactions. We demonstrate that a careful choice of leading- and next-to-leading-order terms in an effective Lagrangian gives rise to a systematic expansion of the T matrix around the resonance, with controlled error estimates. We compare phase shifts and pole positions with those of a toy model. We are extending our EFT to include Coulomb interactions with the goal of describing nuclear resonances, such as those appearing in the scattering of alpha particles. This material is based upon work supported in part by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, under Award Number DE-FG02-04ER41338.

  7. Effect of Tensor Range in Nuclear Two-Body Problems

    DOE R&D Accomplishments Database

    Feshbach, H.; Schwinger, J.; Harr, J. A.

    1949-11-01

    The interaction between neutron and proton in the triplet state is investigated, a wide variation in the values of both central and tensor ranges are included; the per cent D state in the deuteron and the effective triplet range have been computed; the results are applied tot he discussion of the magnetic moment of the deuteron, the photoelectric disintegration of the deuteron, and neutron-proton scattering.

  8. Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation.

    PubMed

    Margottin, F; Benichou, S; Durand, H; Richard, V; Liu, L X; Gomas, E; Benarous, R

    1996-09-15

    The Vpu and CD4 cytoplasmic domains were found, by using a two-hybrid assay in yeast, to interact in the absence of their membrane anchor domains. Studies on several deletion and point mutants revealed that the overall structure of the Vpu cytoplasmic domain is required for this interaction. The Vpu amino acid residues involved in the interaction with CD4 were identified. Deletion of the C-terminal residues of Vpu, required for CD4 degradation, as well as the double mutation on the casein kinase II phosphorylation sites S52N-S56N, also involved in CD4 degradation, resulted in the loss of interaction with CD4 and in the inability to induce CD4 degradation. These results suggest that the ability of Vpu to mediate the degradation of CD4 is linked to its capacity to physically interact with CD4. However, additional mutagenesis on the S52 site revealed that the interaction between the cytoplasmic domains of Vpu and CD4 is not sufficient for in vitro Vpu-mediated CD4 degradation.

  9. Regularization of the collision in the electromagnetic two-body problem.

    PubMed

    Hollander, Efrain Buksman; De Luca, Jayme

    2004-12-01

    We derive a differential equation that is regular at the collision of two equal-mass bodies with attractive interaction in the relativistic action-at-a-distance electrodynamics. We use the energy constant related to the Poincare invariance of the theory to define finite variables with finite derivatives at the collision. The collision orbits are calculated numerically using the regular equation adapted in a self-consistent minimization method (a stable numerical method that chooses only nonrunaway solutions). This dynamical system appeared 100 years ago as an example of covariant time-symmetric two-body dynamics and acquired the status of electrodynamics in the 1940s by the works of Dirac, Wheeler, and Feynman. We outline the method with an emphasis on the physics of this complex conservative dynamical system.

  10. Regularization of the collision in the electromagnetic two-body problem

    NASA Astrophysics Data System (ADS)

    Hollander, Efrain Buksman; De Luca, Jayme

    2004-12-01

    We derive a differential equation that is regular at the collision of two equal-mass bodies with attractive interaction in the relativistic action-at-a-distance electrodynamics. We use the energy constant related to the Poincaré invariance of the theory to define finite variables with finite derivatives at the collision. The collision orbits are calculated numerically using the regular equation adapted in a self-consistent minimization method (a stable numerical method that chooses only nonrunaway solutions). This dynamical system appeared 100 years ago as an example of covariant time-symmetric two-body dynamics and acquired the status of electrodynamics in the 1940s by the works of Dirac, Wheeler, and Feynman. We outline the method with an emphasis on the physics of this complex conservative dynamical system.

  11. Residual meson-meson interaction from lattice gauge simulation in a simple QED{sub 2+1} model

    SciTech Connect

    J. Canosa; H. Fiebig

    1995-08-01

    The residual interaction for a meson-meson system is computed utilizing the cumulant, or cluster, expansion of the momentum-space time correlation matrix. The cumulant expansion serves to define asymptotic, or free, meson-meson operators. The definition of an effective interaction is then based on a comparison of the full (interacting) and the free (noninteracting) time correlation matrices. The proposed method, which may straight forwardly be transcribed to other hadron-hadron systems, here is applied to a simple 2+1 dimensional U(1) lattice gauge model tuned such that it is confining. Fermions are treated in the staggered scheme. The effective interaction exhibits a repulsive core and attraction at intermediate relative distances. These findings are consistent with an earlier study of the same model utilizing L{umlt u}scher's method where scattering phase shifts are obtained directly.

  12. Residue contact-count potentials are as effective as residue-residue contact-type potentials for ranking protein decoys

    PubMed Central

    Bolser, Dan M; Filippis, Ioannis; Stehr, Henning; Duarte, Jose; Lappe, Michael

    2008-01-01

    Background For over 30 years potentials of mean force have been used to evaluate the relative energy of protein structures. The most commonly used potentials define the energy of residue-residue interactions and are derived from the empirical analysis of the known protein structures. However, single-body residue 'environment' potentials, although widely used in protein structure analysis, have not been rigorously compared to these classical two-body residue-residue interaction potentials. Here we do not try to combine the two different types of residue interaction potential, but rather to assess their independent contribution to scoring protein structures. Results A data set of nearly three thousand monomers was used to compare pairwise residue-residue 'contact-type' propensities to single-body residue 'contact-count' propensities. Using a large and standard set of protein decoys we performed an in-depth comparison of these two types of residue interaction propensities. The scores derived from the contact-type and contact-count propensities were assessed using two different performance metrics and were compared using 90 different definitions of residue-residue contact. Our findings show that both types of score perform equally well on the task of discriminating between near-native protein decoys. However, in a statistical sense, the contact-count based scores were found to carry more information than the contact-type based scores. Conclusion Our analysis has shown that the performance of either type of score is very similar on a range of different decoys. This similarity suggests a common underlying biophysical principle for both types of residue interaction propensity. However, several features of the contact-count based propensity suggests that it should be used in preference to the contact-type based propensity. Specifically, it has been shown that contact-counts can be predicted from sequence information alone. In addition, the use of a single-body term allows

  13. HIGH TEMPERATURE INTERACTIONS BETWEEN RESIDUAL OIL ASH AND DISPERSED KAOLINITE POWDERS

    EPA Science Inventory

    The potential use of sorbents to manage ultrafine ash aerosol emissions from residual oil combustion was investigated using a downfired 82-kW-rated laboratory-scale refractory-lined combustor. The major constituents were vanadium (V), iron (Fe), nickel, (Ni) and zinc (Zn). Of the...

  14. HIGH TEMPERATURE INTERACTIONS BETWEEN RESIDUAL OIL ASH AND DISPERSED KAOLINITE POWDERS

    EPA Science Inventory

    The potential use of sorbents to manage ultrafine ash aerosol emissions from residual oil combustion was investigated using a downfired 82-kW-rated laboratory-scale refractory-lined combustor. The major constituents were vanadium (V), iron (Fe), nickel, (Ni) and zinc (Zn). Of the...

  15. Perturbed interaction between residues 85 and 204 in Tyr-185-->Phe and Asp-85-->Glu bacteriorhodopsins.

    PubMed Central

    Richter, H T; Needleman, R; Lanyi, J K

    1996-01-01

    According to earlier reports, residue 85 in the bacteriorhodopsin mutants D85E and Y185F deprotonates with two apparent pKa values. Additionally, in Y185F, Asp-85 becomes significantly more protonated during light adaptation. We provide a new explanation for these findings. It is based on the scheme that links the protonation state of residue 85 to the protonation state of residue 204 (S.P. Balashov, E.S. Imasheva, R. Govindjee, and T.G. Ebrey. 1996. Biophys. J. 70:473-481; H.T. Richter, L.S. Brown, R. Needleman, and J.K. Lanyi. 1996. Biochemistry. 35:4054-4062) and justified by the observation that the biphasic titration curves of D85E and Y185F are converted to monophasic when the E204Q residue change is introduced as a second mutation. Accordingly, the D85E and Y 185F mutations are not the cause of the biphasic titration, as that is a property of the wild-type protein. By perturbing the extracellular region of the protein, the mutations increase the pKa of residue 85. This increases the amplitude of the second titration component and makes the biphasic character of the curves more obvious. Likewise, a small rise in the pKa of Asp-85 when the retinal isomerizes from 13-cis, 15-syn to all-trans accounts for the changed titration behavior of Y185F after light adaptation. This mechanism simplifies and unites the interpretation of what had appeared to be complex and unrelated phenomena. PMID:8968608

  16. Perturbed interaction between residues 85 and 204 in Tyr-185-->Phe and Asp-85-->Glu bacteriorhodopsins.

    PubMed

    Richter, H T; Needleman, R; Lanyi, J K

    1996-12-01

    According to earlier reports, residue 85 in the bacteriorhodopsin mutants D85E and Y185F deprotonates with two apparent pKa values. Additionally, in Y185F, Asp-85 becomes significantly more protonated during light adaptation. We provide a new explanation for these findings. It is based on the scheme that links the protonation state of residue 85 to the protonation state of residue 204 (S.P. Balashov, E.S. Imasheva, R. Govindjee, and T.G. Ebrey. 1996. Biophys. J. 70:473-481; H.T. Richter, L.S. Brown, R. Needleman, and J.K. Lanyi. 1996. Biochemistry. 35:4054-4062) and justified by the observation that the biphasic titration curves of D85E and Y185F are converted to monophasic when the E204Q residue change is introduced as a second mutation. Accordingly, the D85E and Y 185F mutations are not the cause of the biphasic titration, as that is a property of the wild-type protein. By perturbing the extracellular region of the protein, the mutations increase the pKa of residue 85. This increases the amplitude of the second titration component and makes the biphasic character of the curves more obvious. Likewise, a small rise in the pKa of Asp-85 when the retinal isomerizes from 13-cis, 15-syn to all-trans accounts for the changed titration behavior of Y185F after light adaptation. This mechanism simplifies and unites the interpretation of what had appeared to be complex and unrelated phenomena.

  17. A Database of Transition-Metal-Coordinated Peptide Cross-Sections: Selective Interaction with Specific Amino Acid Residues

    NASA Astrophysics Data System (ADS)

    Dilger, Jonathan M.; Glover, Matthew S.; Clemmer, David E.

    2017-07-01

    Ion mobility mass spectrometry (IMS-MS) techniques were used to generate a database of 2288 collision cross sections of transition-metal-coordinated tryptic peptide ions. This database consists of cross sections for 1253 [Pep + X]2+ and 1035 [Pep + X + H]3+, where X2+ corresponds to Mn2+, Co2+, Ni2+, Cu2+, or Zn2+. This number of measurements enables the extraction of structural trends for transition-metal-coordinated peptide ions. The range of structures and changes in collision cross sections for X2+-coordinated species (compared with protonated species of the same charge state) is similar to Mg2+-coordinated species. This suggests that the structures are largely determined by similarities in cation size with differences among the cross section distributions presumably caused by X2+ interactions with specific functional groups offered by the residue R-groups or the peptide backbone. Cross section contributions for individual residues upon X2+ solvation are assessed with the derivation of intrinsic size parameters (ISPs). The comparison of the [Pep + X]2+ ISPs with those previously reported for [Pep + Mg]2+ ions displays a lower contribution to the cross section for His, carboxyamidomethylated Cys, and Met, and is consistent with specific metal-residue interactions identified within protein X-ray crystallography databases.

  18. Identification of important residues of insulin-like peptide 5 and its receptor RXFP4 for ligand-receptor interactions.

    PubMed

    Wang, Xin-Yi; Guo, Yu-Qi; Shao, Xiao-Xia; Liu, Ya-Li; Xu, Zeng-Guang; Guo, Zhan-Yun

    2014-09-15

    Insulin-like peptide 5 (INSL5) is an insulin/relaxin superfamily peptide involved in the regulation of glucose homeostasis by activating its receptor RXFP4, which can also be activated by relaxin-3 in vitro. To determine the interaction mechanism of INSL5 with its receptor RXFP4, we studied their electrostatic interactions using a charge-exchange mutagenesis approach. First, we identified three negatively charged extracellular residues (Glu100, Asp104 and Glu182) in human RXFP4 that were important for receptor activation by wild-type INSL5. Second, we demonstrated that two positively charged B-chain Arg residues (B13Arg and B23Arg) in human INSL5 were involved in receptor binding and activation. Third, we proposed probable electrostatic interactions between INSL5 and RXFP4: the B-chain central B13Arg of INSL5 interacts with both Asp104 and Glu182 of RXFP4, meanwhile the B-chain C-terminal B23Arg of INSL5 interacts with both Glu100 and Asp104 of RXFP4. The present electrostatic interactions between INSL5 and RXFP4 were similar to our previously identified interactions between relaxin-3 and RXFP4, but had subtle differences that might be caused by the different B-chain C-terminal conformations of relaxin-3 and INSL5 because a dipeptide exchange at the B-chain C-terminus significantly decreased the activity of INSL5 and relaxin-3 to receptor RXFP4. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction

    PubMed Central

    Stewart, Chelsea M.; Buffalo, Cosmo Z.; Valderrama, J. Andrés; Henningham, Anna; Cole, Jason N.; Nizet, Victor; Ghosh, Partho

    2016-01-01

    The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A “capture-and-collapse” model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis. PMID:27512043

  20. De novo design of protein-protein interactions through modification of inter-molecular helix-helix interface residues.

    PubMed

    Yagi, Sota; Akanuma, Satoshi; Yamagishi, Manami; Uchida, Tatsuya; Yamagishi, Akihiko

    2016-05-01

    For de novo design of protein-protein interactions (PPIs), information on the shape and chemical complementarity of their interfaces is generally required. Recent advances in computational PPI design have allowed for de novo design of protein complexes, and several successful examples have been reported. In addition, a simple and easy-to-use approach has also been reported that arranges leucines on a solvent-accessible region of an α-helix and places charged residues around the leucine patch to induce interactions between the two helical peptides. For this study, we adopted this approach to de novo design a new PPI between the helical bundle proteins sulerythrin and LARFH. A non-polar patch was created on an α-helix of LARFH around which arginine residues were introduced to retain its solubility. The strongest interaction found was for the LARFH variant cysLARFH-IV-3L3R and the sulerythrin mutant 6L6D (KD=0.16 μM). This artificial protein complex is maintained by hydrophobic and ionic interactions formed by the inter-molecular helical bundle structure. Therefore, by the simple and easy-to-use approach to create de novo interfaces on the α-helices, we successfully generated an artificial PPI. We also created a second LARFH variant with the non-polar patch surrounded by positively charged residues at each end. Upon mixing this LARFH variant with 6L6D, mesh-like fibrous nanostructures were observed by atomic force microscopy. Our method may, therefore, also be applicable to the de novo design of protein nanostructures. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Probing alkali metal–π interactions with the side chain residue of tryptophan

    PubMed Central

    Hu, Jiaxin; Barbour, Leonard J.; Gokel, George W.

    2002-01-01

    Feeble forces play a significant role in the organization of proteins. These include hydrogen bonding, hydrophobic interactions, salt bridge formation, and steric interactions. The alkali metal cation-π interaction is a force of potentially profound importance but its consideration in biology has been limited by the lack of experimental evidence. Our previous studies of cation–π interactions with Na+ and K+ involved the side arms of tryptophan (indole), tyrosine (phenol), and phenylalanine (benzene) as the arene donors. The receptor system possesses limiting steric constraints. In this report, we show that direct interactions between alkali metals and arenes occur at or within the van der Waals contact distance. PMID:11943874

  2. The 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors.

    PubMed Central

    Ariel, N; Ordentlich, A; Barak, D; Bino, T; Velan, B; Shafferman, A

    1998-01-01

    The role of the functional architecture of the human acetylcholinesterase (HuAChE) active centre in accommodating the non-covalent inhibitors tacrine and huperzine A, or the carbamates pyridostigmine and physostigmine, was analysed using 16 mutants of residues lining the active-centre gorge. Despite the structural diversity of the ligands, certain common properties of the complexes could be observed: (a) replacement of aromatic residues Tyr133, Tyr337 and especially Trp86, resulted in pronounced changes in stability of all the complexes examined; (b) effects due to replacements of the five other aromatic residues along the active-centre gorge, such as the acyl pocket (Phe295, Phe297) or at the peripheral anionic site (Tyr124, Trp286, Tyr341) were relatively small; (c) effects due to substitution of the carboxylic residues in the gorge (Glu202, Glu450) were moderate. These results and molecular modelling indicate that the aromatic side chains of residues Trp86, Tyr133 and Tyr337 form together a continuous 'aromatic patch' lining the wall of the active-centre gorge, allowing for the accommodation of the different ligands via multiple modes of interaction. Studies with HuAChE mutants carrying replacements at positions 86, 133 and 337 indicate that the orientations of huperzine A and tacrine in the HuAChE complexes in solution are significantly different from those observed in X-ray structures of the corresponding complexes with Torpedo californica AChE (TcAChE). These discrepancies may be explained in terms of structural differences between the complexes of HuAChE and TcAChE or, more likely, by the enhanced flexibility of the AChE active-centre gorge in solution as compared with the crystalline state. PMID:9742217

  3. The 'aromatic patch' of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors.

    PubMed

    Ariel, N; Ordentlich, A; Barak, D; Bino, T; Velan, B; Shafferman, A

    1998-10-01

    The role of the functional architecture of the human acetylcholinesterase (HuAChE) active centre in accommodating the non-covalent inhibitors tacrine and huperzine A, or the carbamates pyridostigmine and physostigmine, was analysed using 16 mutants of residues lining the active-centre gorge. Despite the structural diversity of the ligands, certain common properties of the complexes could be observed: (a) replacement of aromatic residues Tyr133, Tyr337 and especially Trp86, resulted in pronounced changes in stability of all the complexes examined; (b) effects due to replacements of the five other aromatic residues along the active-centre gorge, such as the acyl pocket (Phe295, Phe297) or at the peripheral anionic site (Tyr124, Trp286, Tyr341) were relatively small; (c) effects due to substitution of the carboxylic residues in the gorge (Glu202, Glu450) were moderate. These results and molecular modelling indicate that the aromatic side chains of residues Trp86, Tyr133 and Tyr337 form together a continuous 'aromatic patch' lining the wall of the active-centre gorge, allowing for the accommodation of the different ligands via multiple modes of interaction. Studies with HuAChE mutants carrying replacements at positions 86, 133 and 337 indicate that the orientations of huperzine A and tacrine in the HuAChE complexes in solution are significantly different from those observed in X-ray structures of the corresponding complexes with Torpedo californica AChE (TcAChE). These discrepancies may be explained in terms of structural differences between the complexes of HuAChE and TcAChE or, more likely, by the enhanced flexibility of the AChE active-centre gorge in solution as compared with the crystalline state.

  4. Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion

    PubMed Central

    Zeng, Xiancheng; Mukhopadhyay, Suchetana; Brooks, Charles L.

    2015-01-01

    Alphavirus envelope proteins, organized as trimers of E2–E1 heterodimers on the surface of the pathogenic alphavirus, mediate the low pH-triggered fusion of viral and endosomal membranes in human cells. The lack of specific treatment for alphaviral infections motivates our exploration of potential antiviral approaches by inhibiting one or more fusion steps in the common endocytic viral entry pathway. In this work, we performed constant pH molecular dynamics based on an atomic model of the alphavirus envelope with icosahedral symmetry. We have identified pH-sensitive residues that cause the largest shifts in thermodynamic driving forces under neutral and acidic pH conditions for various fusion steps. A series of conserved interdomain His residues is identified to be responsible for the pH-dependent conformational changes in the fusion process, and ligand binding sites in their vicinity are anticipated to be potential drug targets aimed at inhibiting viral infections. PMID:25646410

  5. Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.

    PubMed

    Zeng, Xiancheng; Mukhopadhyay, Suchetana; Brooks, Charles L

    2015-02-17

    Alphavirus envelope proteins, organized as trimers of E2-E1 heterodimers on the surface of the pathogenic alphavirus, mediate the low pH-triggered fusion of viral and endosomal membranes in human cells. The lack of specific treatment for alphaviral infections motivates our exploration of potential antiviral approaches by inhibiting one or more fusion steps in the common endocytic viral entry pathway. In this work, we performed constant pH molecular dynamics based on an atomic model of the alphavirus envelope with icosahedral symmetry. We have identified pH-sensitive residues that cause the largest shifts in thermodynamic driving forces under neutral and acidic pH conditions for various fusion steps. A series of conserved interdomain His residues is identified to be responsible for the pH-dependent conformational changes in the fusion process, and ligand binding sites in their vicinity are anticipated to be potential drug targets aimed at inhibiting viral infections.

  6. Two-body problem for two-dimensional electrons in the Bernervig-Hughes-Zhang model

    NASA Astrophysics Data System (ADS)

    Sablikov, Vladimir A.

    2017-02-01

    We study the two-body problem for two-dimensional electron systems in a symmetrized Bernevig-Hughes-Zhang model, which is widely used to describe topological and conventional insulators. The main result is that two interacting electrons can form bound states with the energy in the gap of the band spectrum. The pairing mechanism can be interpreted as the formation of a negative reduced effective mass of two electrons. The problem is complicated because the relative motion of the electrons is coupled to the center-of-mass motion. We consider the case of zero total momentum. Detail calculations are carried out for the repulsive interaction potential of steplike form. The states are classified according to their spin structure and two-particle basis functions that form a given bound state. We analyze the spectra and electronic structure of the bound states in the case of both topological and trivial phases and especially focus on effects originating from the band inversion and the coupling of the electron and hole bands. In the trivial phase and the topological phase with the large coupling parameter a , the bound state spectra are qualitatively similar. However, when a is less a certain value, the situation changes dramatically. In the topological phase, new states arise with a higher binding energy at lower interaction potential, which evidences that the band inversion can favor pairing the electrons.

  7. Electromagnetic two-body problem: recurrent dynamics in the presence of state-dependent delay

    NASA Astrophysics Data System (ADS)

    De Luca, Jayme; Guglielmi, Nicola; Humphries, Tony; Politi, Antonio

    2010-05-01

    We study the electromagnetic two-body problem of classical electrodynamics as a prototype dynamical system with state-dependent delays. The equations of motion are analysed with reference to motion along a straight line in the presence of an electrostatic field. We consider the general electromagnetic equations of motion for point charges with advanced and retarded interactions and study two limits, (a) retarded-only interactions (Dirac electrodynamics) and (b) half-retarded plus half-advanced interactions (Wheeler-Feynman electrodynamics). A fixed point is created where the electrostatic field balances the Coulombian attraction, and we use local analysis near this fixed point to derive necessary conditions for a Hopf bifurcation. In case (a), we study a Hopf bifurcation about an unphysical fixed point and find that it is subcritical. In case (b), there is a Hopf bifurcation about a physical fixed point and we study several families of periodic orbits near this point. The bifurcating periodic orbits are illustrated and simulated numerically, by introducing a surrogate dynamical system into the numerical analysis which transforms future data into past data by exploiting the periodicity, thus obtaining systems with only delays.

  8. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    PubMed Central

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  9. Standardization of a Volumetric Displacement Measurement for Two-Body Abrasion Scratch Test Data Analysis

    NASA Technical Reports Server (NTRS)

    Street, K. W. Jr.; Kobrick, R. L.; Klaus, D. M.

    2011-01-01

    A limitation has been identified in the existing test standards used for making controlled, two-body abrasion scratch measurements based solely on the width of the resultant score on the surface of the material. A new, more robust method is proposed for analyzing a surface scratch that takes into account the full three-dimensional profile of the displaced material. To accomplish this, a set of four volume- displacement metrics was systematically defined by normalizing the overall surface profile to denote statistically the area of relevance, termed the Zone of Interaction. From this baseline, depth of the trough and height of the plowed material are factored into the overall deformation assessment. Proof-of-concept data were collected and analyzed to demonstrate the performance of this proposed methodology. This technique takes advantage of advanced imaging capabilities that allow resolution of the scratched surface to be quantified in greater detail than was previously achievable. When reviewing existing data analysis techniques for conducting two-body abrasive scratch tests, it was found that the ASTM International Standard G 171 specified a generic metric based only on visually determined scratch width as a way to compare abraded materials. A limitation to this method was identified in that the scratch width is based on optical surface measurements, manually defined by approximating the boundaries, but does not consider the three-dimensional volume of material that was displaced. With large, potentially irregular deformations occurring on softer materials, it becomes unclear where to systematically determine the scratch width. Specifically, surface scratches on different samples may look the same from a top view, resulting in an identical scratch width measurement, but may vary in actual penetration depth and/or plowing deformation. Therefore, two different scratch profiles would be measured as having identical abrasion properties, although they differ

  10. Feasibility of Using Electrocochleography for Objective Estimation of Electro-Acoustic Interactions in Cochlear Implant Recipients with Residual Hearing

    PubMed Central

    Koka, Kanthaiah; Litvak, Leonid M.

    2017-01-01

    Although cochlear implants (CI) traditionally have been used to treat individuals with bilateral profound sensorineural hearing loss, a recent trend is to implant individuals with residual low-frequency hearing. Patients who retain some residual acoustic hearing after surgery often can benefit from electro-acoustic stimulation (EAS) technologies, which combine conventional acoustic amplification with electrical stimulation. However, interactions between acoustic and electrical stimulation may affect outcomes adversely and are time-consuming and difficult to assess behaviorally. This study demonstrated the feasibility of using the Advanced Bionics HiRes90K Advantage implant electronics and HiFocus Mid Scala/1j electrode to measure electrocochleography (ECochG) responses in the presence of electrical stimulation to provide an objective estimate of peripheral physiologic EAS interactions. In general, electrical stimulation reduced ECochG response amplitudes to acoustic stimulation. The degree of peripheral EAS interaction varied as a function of acoustic pure tone frequency and the intra-cochlear location of the electrically stimulated electrode. Further development of this technique may serve to guide and optimize clinical EAS system fittings in the future. PMID:28674482

  11. Prediction of fatty acid-binding residues on protein surfaces with three-dimensional probability distributions of interacting atoms.

    PubMed

    Mahalingam, Rajasekaran; Peng, Hung-Pin; Yang, An-Suei

    2014-08-01

    Protein-fatty acid interaction is vital for many cellular processes and understanding this interaction is important for functional annotation as well as drug discovery. In this work, we present a method for predicting the fatty acid (FA)-binding residues by using three-dimensional probability density distributions of interacting atoms of FAs on protein surfaces which are derived from the known protein-FA complex structures. A machine learning algorithm was established to learn the characteristic patterns of the probability density maps specific to the FA-binding sites. The predictor was trained with five-fold cross validation on a non-redundant training set and then evaluated with an independent test set as well as on holo-apo pair's dataset. The results showed good accuracy in predicting the FA-binding residues. Further, the predictor developed in this study is implemented as an online server which is freely accessible at the following website, http://ismblab.genomics.sinica.edu.tw/.

  12. Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction

    PubMed Central

    Lipska, Agnieszka G.; Sieradzan, Adam K.; Giełdoń, Artur; Liwo, Adam; Scheraga, Harold A.

    2016-01-01

    The folding of the N-terminal part of the B-domain of staphylococcal protein A (PDB ID: 1BDD, a 46-residue three-α-helix bundle) and the formin-binding protein 28 WW domain (PDB ID: 1E0L, a 37-residue three-stranded anti-parallel β protein) was studied by means of Langevin dynamics with the coarse-grained UNRES force field to assess the influence of hydrodynamic interactions on protein-folding pathways and kinetics. The unfolded, intermediate, and native-like structures were identified by cluster analysis, and multi-exponential functions were fitted to the time dependence of the fractions of native and intermediate structures, respectively, to determine bulk kinetics. It was found that introducing hydrodynamic interactions slows down both the formation of an intermediate state and the transition from the collapsed structures to the final native-like structures by creating multiple kinetic traps. Therefore, introducing hydrodynamic interactions considerably slows the folding, as opposed to the results obtained from earlier studies with the use of Gō-like models. PMID:27179474

  13. Drosophila sperm surface alpha-L-fucosidase interacts with the egg coats through its core fucose residues.

    PubMed

    Intra, Jari; Concetta, Veltri; Daniela, De Caro; Perotti, Maria Elisa; Pasini, Maria Enrica

    2015-08-01

    Sperm-oocyte interaction during fertilization is multiphasic, with multicomponent events, taking place between egg's glycoproteins and sperm surface receptors. Protein-carbohydrate complementarities in gamete recognition have observed in cases throughout the whole evolutionary scale. Sperm-associated α-L-fucosidases have been identified in various organisms. Their wide distribution and known properties reflect the hypothesis that fucose and α-L-fucosidases have fundamental function(s) during gamete interactions. An α-L-fucosidase has been detected as transmembrane protein on the surface of spermatozoa of eleven species across the genus Drosophila. Immunofluorescence labeling showed that the protein is localized in the sperm plasma membrane over the acrosome and the tail, in Drosophila melanogaster. In the present study, efforts were made to analyze with solid phase assays the oligosaccharide recognition ability of fruit fly sperm α-L-fucosidase with defined carbohydrate chains that can functionally mimic egg glycoconjugates. Our results showed that α-L-fucosidase bound to fucose residue and in particular it prefers N-glycans carrying core α1,6-linked fucose and core α1,3-linked fucose in N-glycans carrying only a terminal mannose residue. The ability of sperm α-L-fucosidase to bind to the micropylar chorion and to the vitelline envelope was examined in in vitro assays in presence of α-L-fucosidase, either alone or in combination with molecules containing fucose residues. No binding was detected when α-L-fucosidase was pre-incubated with fucoidan, a polymer of α-L-fucose and the monosaccharide fucose. Furthermore, egg labeling with anti-horseradish peroxidase, that recognized only core α1,3-linked fucose, correlates with α-L-fucosidase micropylar binding. Collectively, these data support the hypothesis of the potential role of this glycosidase in sperm-egg interactions in Drosophila.

  14. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans

    PubMed Central

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2011-01-01

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3–5 of each block. Following the first drug administration, the methamphetamine–alcohol combination produced greater elevations of heart rate and ratings of “good drug effect” compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination. PMID:21748253

  15. Complete characterization of the ground-space structure of two-body frustration-free Hamiltonians for qubits

    SciTech Connect

    Ji Zhengfeng; Wei Zhaohui; Zeng Bei

    2011-10-15

    The problem of finding the ground state of a frustration-free Hamiltonian carrying only two-body interactions between qubits is known to be solvable in polynomial time. It is also shown recently that, for any such Hamiltonian, there is always a ground state that is a product of single- or two-qubit states. However, it remains unclear whether the whole ground space is of any succinct structure. Here, we give a complete characterization of the ground space of any two-body frustration-free Hamiltonian of qubits. Namely, it is a span of tree tensor network states of the same tree structure. This characterization allows us to show that the problem of determining the ground-state degeneracy is as hard as, but no harder than, its classical analog.

  16. Two hydrophobic residues can determine the specificity of mitogen-activated protein kinase docking interactions.

    PubMed

    Bardwell, A Jane; Bardwell, Lee

    2015-10-30

    MAPKs bind to many of their upstream regulators and downstream substrates via a short docking motif (the D-site) on their binding partner. MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. Here we demonstrate that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. Changing just 1 or 2 key hydrophobic residues in this submotif is sufficient to turn a weak JNK-binding D-site into a strong one, or vice versa. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Moreover, swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK, as predicted. These results provide new insights into docking specificity and suggest that this specificity can evolve rapidly by changes to just 1 or 2 amino acids. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Two Hydrophobic Residues Can Determine the Specificity of Mitogen-activated Protein Kinase Docking Interactions*

    PubMed Central

    Bardwell, A. Jane; Bardwell, Lee

    2015-01-01

    MAPKs bind to many of their upstream regulators and downstream substrates via a short docking motif (the D-site) on their binding partner. MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. Here we demonstrate that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. Changing just 1 or 2 key hydrophobic residues in this submotif is sufficient to turn a weak JNK-binding D-site into a strong one, or vice versa. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Moreover, swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK, as predicted. These results provide new insights into docking specificity and suggest that this specificity can evolve rapidly by changes to just 1 or 2 amino acids. PMID:26370088

  18. Experimental study of the two-body spin-orbit force in nuclei.

    PubMed

    Burgunder, G; Sorlin, O; Nowacki, F; Giron, S; Hammache, F; Moukaddam, M; de Séréville, N; Beaumel, D; Càceres, L; Clément, E; Duchêne, G; Ebran, J P; Fernandez-Dominguez, B; Flavigny, F; Franchoo, S; Gibelin, J; Gillibert, A; Grévy, S; Guillot, J; Lepailleur, A; Matea, I; Matta, A; Nalpas, L; Obertelli, A; Otsuka, T; Pancin, J; Poves, A; Raabe, R; Scarpaci, J A; Stefan, I; Stodel, C; Suzuki, T; Thomas, J C

    2014-01-31

    Energies and spectroscopic factors of the first 7/2-, 3/2-, 1/2-, and 5/2- states in the (35)Si21 nucleus were determined by means of the (d, p) transfer reaction in inverse kinematics at GANIL using the MUST2 and EXOGAM detectors. By comparing the spectroscopic information on the Si35 and S37 isotones, a reduction of the p3/2-p1/2 spin-orbit splitting by about 25% is proposed, while the f7/2-f5/2 spin-orbit splitting seems to remain constant. These features, derived after having unfolded nuclear correlations using shell model calculations, have been attributed to the properties of the two-body spin-orbit interaction, the amplitude of which is derived for the first time in an atomic nucleus. The present results, remarkably well reproduced by using several realistic nucleon-nucleon forces, provide a unique touchstone for the modeling of the spin-orbit interaction in atomic nuclei.

  19. Experimental Study of the Two-Body Spin-Orbit Force in Nuclei

    NASA Astrophysics Data System (ADS)

    Burgunder, G.; Sorlin, O.; Nowacki, F.; Giron, S.; Hammache, F.; Moukaddam, M.; de Séréville, N.; Beaumel, D.; Càceres, L.; Clément, E.; Duchêne, G.; Ebran, J. P.; Fernandez-Dominguez, B.; Flavigny, F.; Franchoo, S.; Gibelin, J.; Gillibert, A.; Grévy, S.; Guillot, J.; Lepailleur, A.; Matea, I.; Matta, A.; Nalpas, L.; Obertelli, A.; Otsuka, T.; Pancin, J.; Poves, A.; Raabe, R.; Scarpaci, J. A.; Stefan, I.; Stodel, C.; Suzuki, T.; Thomas, J. C.

    2014-01-01

    Energies and spectroscopic factors of the first 7/2-, 3/2-, 1/2-, and 5/2- states in the Si2135 nucleus were determined by means of the (d, p) transfer reaction in inverse kinematics at GANIL using the MUST2 and EXOGAM detectors. By comparing the spectroscopic information on the Si35 and S37 isotones, a reduction of the p3/2-p1/2 spin-orbit splitting by about 25% is proposed, while the f7/2-f5/2 spin-orbit splitting seems to remain constant. These features, derived after having unfolded nuclear correlations using shell model calculations, have been attributed to the properties of the two-body spin-orbit interaction, the amplitude of which is derived for the first time in an atomic nucleus. The present results, remarkably well reproduced by using several realistic nucleon-nucleon forces, provide a unique touchstone for the modeling of the spin-orbit interaction in atomic nuclei.

  20. Standardization of a Volumetric Displacement Measurement for Two-Body Abrasion Scratch Test Data Analysis

    NASA Technical Reports Server (NTRS)

    Kobrick, Ryan L.; Klaus, David M.; Street, Kenneth W., Jr.

    2010-01-01

    A limitation has been identified in the existing test standards used for making controlled, two-body abrasion scratch measurements based solely on the width of the resultant score on the surface of the material. A new, more robust method is proposed for analyzing a surface scratch that takes into account the full three-dimensional profile of the displaced material. To accomplish this, a set of four volume displacement metrics are systematically defined by normalizing the overall surface profile to statistically denote the area of relevance, termed the Zone of Interaction (ZOI). From this baseline, depth of the trough and height of the ploughed material are factored into the overall deformation assessment. Proof of concept data were collected and analyzed to demonstrate the performance of this proposed methodology. This technique takes advantage of advanced imaging capabilities that now allow resolution of the scratched surface to be quantified in greater detail than was previously achievable. A quantified understanding of fundamental particle-material interaction is critical to anticipating how well components can withstand prolonged use in highly abrasive environments, specifically for our intended applications on the surface of the Moon and other planets or asteroids, as well as in similarly demanding, harsh terrestrial settings

  1. The interactive effect of fungicide residues and yeast assimilable nitrogen on fermentation kinetics and hydrogen sulfide production during cider fermentation.

    PubMed

    Boudreau, Thomas F; Peck, Gregory M; O'Keefe, Sean F; Stewart, Amanda C

    2017-01-01

    Fungicide residues on fruit may adversely affect yeast during cider fermentation, leading to sluggish or stuck fermentation or the production of hydrogen sulfide (H2 S), which is an undesirable aroma compound. This phenomenon has been studied in grape fermentation but not in apple fermentation. Low nitrogen availability, which is characteristic of apples, may further exacerbate the effects of fungicides on yeast during fermentation. The present study explored the effects of three fungicides: elemental sulfur (S(0) ) (known to result in increased H2 S in wine); fenbuconazole (used in orchards but not vineyards); and fludioxonil (used in post-harvest storage of apples). Only S(0) led to increased H2 S production. Fenbuconazole (≥0.2 mg L(-1) ) resulted in a decreased fermentation rate and increased residual sugar. An interactive effect of yeast assimilable nitrogen (YAN) concentration and fenbuconazole was observed such that increasing the YAN concentration alleviated the negative effects of fenbuconazole on fermentation kinetics. Cidermakers should be aware that residual fenbuconazole (as low as 0.2 mg L(-1) ) in apple juice may lead to stuck fermentation, especially when the YAN concentration is below 250 mg L(-1) . These results indicate that fermentation problems attributed to low YAN may be caused or exacerbated by additional factors such as fungicide residues, which have a greater impact on fermentation performance under low YAN conditions. © 2016 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2016 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  2. MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) for identifying protein–ligand fragment interaction, pathways and SNPs

    PubMed Central

    Tanramluk, Duangrudee; Narupiyakul, Lalita; Akavipat, Ruj; Gong, Sungsam; Charoensawan, Varodom

    2016-01-01

    Protein–ligand interaction analysis is an important step of drug design and protein engineering in order to predict the binding affinity and selectivity between ligands to the target proteins. To date, there are more than 100 000 structures available in the Protein Data Bank (PDB), of which ∼30% are protein–ligand (MW below 1000 Da) complexes. We have developed the integrative web server MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) with the aim of providing a user-friendly web interface to assist structural study and design of protein–ligand interactions. In brief, the server allows the users to input the chemical fragments and present all the unique molecular interactions to the target proteins with available three-dimensional structures in the PDB. The users can also link the ligands of interest to assess possible off-target proteins, human variants and pathway information using our all-in-one integrated tools. Taken together, we envisage that the server will facilitate and improve the study of protein–ligand interactions by allowing observation and comparison of ligand interactions with multiple proteins at the same time. (http://manoraa.org). PMID:27131358

  3. Functions of key residues in the ligand-binding pocket of vitamin D receptor: Fragment molecular orbital interfragment interaction energy analysis

    NASA Astrophysics Data System (ADS)

    Yamagishi, Kenji; Yamamoto, Keiko; Yamada, Sachiko; Tokiwa, Hiroaki

    2006-03-01

    Fragment molecular orbital-interfragment interaction energy calculations of the vitamin D receptor (VDR)/1α,25-dihydroxyvitamin D 3 complex were utilized to assign functions of key residues of the VDR. Only one residue forms a significant interaction with the corresponding hydroxy group of the ligand, although two residues are located around each hydroxy group. The degradation of binding affinity for derivatives upon removal of a hydroxy group is closely related to the trend in the strength of the hydrogen bonds. Type II hereditary rickets due to an Arg274 point mutation is caused by the lack of the strongest hydrogen bond.

  4. The F13 residue is critical for interaction among the coat protein subunits of papaya mosaic virus.

    PubMed

    Laliberté Gagné, M E; Lecours, K; Gagné, S; Leclerc, D

    2008-04-01

    Papaya mosaic virus (PapMV) coat protein (CP) in Escherichia coli was previously showed to self-assemble in nucleocapsid-like particles (NLPs) that were similar in shape and appearance to the native virus. We have also shown that a truncated CP missing the N-terminal 26 amino acids is monomeric and loses its ability to bind RNA. It is likely that the N-terminus of the CP is important for the interaction between the subunits in self-assembly into NLPs. In this work, through deletion and mutation analysis, we have shown that the deletion of 13 amino acids is sufficient to generate the monomeric form of the CP. Furthermore, we have shown that residue F13 is critical for self-assembly of the CP subunits into NLPs. The replacement of F13 with hydrophobic residues (L or Y) generated mutated forms of the CP that were able to self-assemble into NLPs. However, the replacement of F13 by A, G, R, E or S was detrimental to the self-assembly of the protein into NLPs. We concluded that a hydrophobic interaction at the N-terminus is important to ensure self-assembly of the protein into NLPs. We also discuss the importance of F13 for assembly of other members of the potexvirus family.

  5. Interaction with specific HSP90 residues as a scoring function: validation in the D3R Grand Challenge 2015

    NASA Astrophysics Data System (ADS)

    Santos-Martins, Diogo

    2016-09-01

    Here is reported the development of a novel scoring function that performs remarkably well at identifying the native binding pose of a subset of HSP90 inhibitors containing aminopyrimidine or resorcinol based scaffolds. This scoring function is called PocketScore, and consists of the interaction energy between a ligand and three residues in the binding pocket: Asp93, Thr184 and a water molecule. We integrated PocketScore into a molecular docking workflow, and used it to participate in the Drug Design Data Resource (D3R) Grand Challenge 2015 (GC2015). PocketScore was able to rank 180 molecules of the GC2015 according to their binding affinity with satisfactory performance. These results indicate that the specific residues considered by PocketScore are determinant to properly model the interaction between HSP90 and its subset of inhibitors containing aminopyrimidine or resorcinol based scaffolds. Moreover, the development of PocketScore aimed at improving docking power while neglecting the prediction of binding affinities, suggesting that accurate identification of native binding poses is a determinant factor for the performance of virtual screens.

  6. Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitro.

    PubMed

    Kovac, Suzana; Ferrand, Audrey; Estève, Jean-Pierre; Mason, Anne B; Baldwin, Graham S

    2009-09-01

    Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin-gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin-ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8-10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo.

  7. Structural polymorphism of human islet amyloid polypeptide (hIAPP) oligomers highlights the importance of interfacial residue interactions.

    PubMed

    Zhao, Jun; Yu, Xiang; Liang, Guizhao; Zheng, Jie

    2011-01-10

    A 37-residue of human islet amyloid polypeptide (hIAPP or amylin) is a main component of amyloid plaques found in the pancreas of ∼90% of type II diabetes patients. It is reported that hIAPP oligomers, rather than mature fibrils, are major toxic species responsible for pancreatic islet β-cell dysfunction and even cell death, but molecular structures of these oligomers remain elusive. In this work, on the basis of recent solid-state NMR and mass-per-length (MPL) data, we model a series of hIAPP oligomers with different β-layers (one, two, and three layers), symmetries (symmetry and asymmetry), and associated interfaces using molecular dynamics simulations. Three distinct interfaces formed by C-terminal β-sheet and C-terminal β-sheet (CC), N-terminal β-sheet and N-terminal β-sheet (NN), and C-terminal β-sheet and N-terminal β-sheet (CN) are identified to drive multiple cross-β-layers laterally associated together to form different amyloid organizations via different intermolecular interactions, in which the CC interface is dominated by polar interactions, the NN interface is dominated by hydrophobic interactions, and the CN interface is dominated by mixed polar and hydrophobic interactions. Overall, the structural stability of the proposed hIAPP oligomers is a result of delicate balance between maximization of favorable peptide-peptide interactions at the interfaces and optimization of solvation energy with globular structure. Different hIAPP oligomeric models indicate a general and intrinsic nature of amyloid polymorphism, driven by different interfacial side-chain interactions. The proposed models are compatible with recent experimental data in overall size, cross-section area, and molecular weight. A general hIAPP aggregation mechanism is proposed on the basis of our simulated models and experimental data.

  8. PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

    SciTech Connect

    Lim, So-Hee; Moon, Jeonghee; Lee, Myungkyu; Lee, Jae-Ran

    2013-09-13

    Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified as a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1.

  9. Selective determination of thiram residues in fruit and vegetables by hydrophilic interaction LC-MS.

    PubMed

    Ringli, Daniela; Schwack, Wolfgang

    2013-01-01

    Thiram belongs to the most important class of dithiocarbamate (DTC) fungicides including dimethyldithiocarbamates (DMDs), ethylenebis(dithiocarbamtes) (EBDs) and propylenebis(dithiocarbamates) (PBDs). During the surface extraction of fruit and vegetables for the LC-MS determination of residues of DMDs, EBDs and PBDs, thiram is reduced by the penicillamine buffer to the DMD anion, thus resulting in false-positive findings of DMD fungicides like ziram. Therefore, an alkaline sulfite buffer was applied for surface extraction, quantitatively transforming thiram into the DMD anion and a stable DMD-sulfite adduct that was used as a selective marker for thiram. Separation was performed isocratically on a ZIC-pHILIC column with acetonitrile-10 mM ammonium hydroxide solution (85/15). Mass selective detection was carried out on a single-quadrupole mass spectrometer coupled to an electrospray ionisation interface operating in negative mode. Using d12-thiram as the internal standard, recoveries of 80-108% were obtained from apples, tomatoes, grapes and sweet peppers, spiked in the range of 0.02-1 mg kg(-1). Limits of detection and quantification were 0.6 and 2 µg kg(-1), respectively.

  10. Lorentz Boosted Potential for a Two-Body System with Unequal Masses

    NASA Astrophysics Data System (ADS)

    Kamada, H.; Polyzou, W. N.; Witała, H.; Miyagawa, K.

    2014-04-01

    We produce a Lorentz boosted two-body potential for particles of different mass that is phase equivalent to a given realistic non-relativistic two-body potential. The relativistic potential is related to the nonrelativistic potential using the Coester-Pieper-Serduke scheme, which ensures that the same scattering wave functions are obtained from the relativistic and non-relativistic potentials. This implies that the phase shifts are identical functions of the relative momentum. To construct the potential we use an iterative scheme that generalizes one that has been applied successfully to two-body systems with equal masses.

  11. Solving the two-body, bound-state Bethe-Salpeter equation

    NASA Astrophysics Data System (ADS)

    Mainland, G. B.

    2003-11-01

    By expanding the solution of the the two-body, bound-state Bethe-Salpeter equation in terms of basis functions that obey the boundary conditions, solutions can be obtained to some, if not many, equations that have heretofore proved intractable. The utility of choosing such basis functions is demonstrated by calculating the zero-energy, bound-state solutions of a spin-0 boson and a spin-1/2 fermion with unequal masses that interact via scalar electrodynamics and are described by the Bethe-Salpeter equation in the ladder approximation. The equation is solved by first making a Wick rotation and then projecting four-dimensional Euclidean space onto the surface of a unit, five-dimensional sphere. Solutions are expanded in terms of basis functions, each of which obeys the boundary conditions and can be expressed in terms of hyperspherical harmonics in five-dimensional space. The Bethe-Salpeter equation is discretized by requiring that the coefficient of each hyperspherical harmonic vanish. All integrations are performed analytically, yielding a generalized matrix eigenvalue equation that is solved numerically. Although the Bethe-Salpeter equation is separable in the zero-energy limit, the feature of Bethe-Salpeter equations that often prevents solutions from being obtained numerically is still present in the equation that is solved.

  12. Two-Body Electrodisintegration of $^3$He at High Momentum Transfer

    SciTech Connect

    R. Schiavilla; O. Benhar; A. Kievsky; L.E. Marcucci; M. Viviani

    2005-08-01

    The {sup 3}He (e,e{prime}p)d reaction is studied using an accurate three-nucleon bound state wave function, a model for the electromagnetic current operator including one- and two-body terms, and the Glauber approximation for the treatment of final state interactions. In contrast to earlier studies, the profile operator in the Glauber expansion is derived from a nucleon-nucleon scattering amplitude, which retains its full spin and isospin dependence and is consistent with phase-shift analyses of two-nucleon scattering data. The amplitude is boosted from the center-of-mass frame, where parameterizations for it are available, to the frame where rescattering occurs. Exact Monte Carlo methods are used to evaluate the relevant matrix elements of the electromagnetic current operator. The predicted cross section is found to be in quantitative agreement with the experimental data for values of the missing momentum p{sub m} in the range (0--700) MeV/c, but underestimates the data at p{sub m} {approx} 1 GeV/c by about a factor of two. However, the longitudinal-transverse asymmetry, measured up to p{sub m} {approx} 600 MeV/c, is well reproduced by theory. A critical comparison is carried out between the results obtained in the present work and those of earlier studies.

  13. Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis

    NASA Astrophysics Data System (ADS)

    Anwar, Muhammad Ayaz; Choi, Sangdun

    2017-03-01

    Toll-like receptor 4 (TLR4), a vital innate immune receptor present on cell surfaces, initiates a signaling cascade during danger and bacterial intrusion. TLR4 needs to form a stable hexamer complex, which is necessary to dimerize the cytoplasmic domain. However, D299G and T399I polymorphism may abrogate the stability of the complex, leading to compromised TLR4 signaling. Crystallography provides valuable insights into the structural aspects of the TLR4 ectodomain; however, the dynamic behavior of polymorphic TLR4 is still unclear. Here, we employed molecular dynamics simulations (MDS), as well as principal component and residue network analyses, to decipher the structural aspects and signaling propagation associated with mutations in TLR4. The mutated complexes were less cohesive, displayed local and global variation in the secondary structure, and anomalous decay in rotational correlation function. Principal component analysis indicated that the mutated complexes also exhibited distinct low-frequency motions, which may be correlated to the differential behaviors of these TLR4 variants. Moreover, residue interaction networks (RIN) revealed that the mutated TLR4/myeloid differentiation factor (MD) 2 complex may perpetuate abnormal signaling pathways. Cumulatively, the MDS and RIN analyses elucidated the mutant-specific conformational alterations, which may help in deciphering the mechanism of loss-of-function mutations.

  14. Residues of the UL25 protein of herpes simplex virus that are required for its stable interaction with capsids.

    PubMed

    Cockrell, Shelley K; Huffman, Jamie B; Toropova, Katerina; Conway, James F; Homa, Fred L

    2011-05-01

    The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated recombinant viruses with either small truncations or amino acid substitutions in the UL25 N terminus. Studies of these mutants demonstrated that there are two important regions within the capsid binding domain. The first 27 amino acids are essential for capsid binding of UL25, while residues 26 to 39, which are highly conserved in the UL25 homologues of other alphaherpesviruses, were found to be critical for stable capsid binding. Cryo-electron microscopy reconstructions of capsids containing either a small tag on the N terminus of UL25 or the green fluorescent protein (GFP) fused between amino acids 50 and 51 of UL25 demonstrate that residues 1 to 27 of UL25 contact the hexon adjacent to the penton. A second region, most likely centered on amino acids 26 to 39, contacts the triplex that is one removed from the penton. Importantly, both of these UL25 capsid binding regions are essential for the stable packaging of full-length viral genomes.

  15. Residues of the UL25 Protein of Herpes Simplex Virus That Are Required for Its Stable Interaction with Capsids ▿

    PubMed Central

    Cockrell, Shelley K.; Huffman, Jamie B.; Toropova, Katerina; Conway, James F.; Homa, Fred L.

    2011-01-01

    The herpes simplex virus 1 (HSV-1) UL25 gene product is a minor capsid component that is required for encapsidation, but not cleavage, of replicated viral DNA. UL25 is located on the capsid surface in a proposed heterodimer with UL17, where five copies of the heterodimer are found at each of the capsid vertices. Previously, we demonstrated that amino acids 1 to 50 of UL25 are essential for its stable interaction with capsids. To further define the UL25 capsid binding domain, we generated recombinant viruses with either small truncations or amino acid substitutions in the UL25 N terminus. Studies of these mutants demonstrated that there are two important regions within the capsid binding domain. The first 27 amino acids are essential for capsid binding of UL25, while residues 26 to 39, which are highly conserved in the UL25 homologues of other alphaherpesviruses, were found to be critical for stable capsid binding. Cryo-electron microscopy reconstructions of capsids containing either a small tag on the N terminus of UL25 or the green fluorescent protein (GFP) fused between amino acids 50 and 51 of UL25 demonstrate that residues 1 to 27 of UL25 contact the hexon adjacent to the penton. A second region, most likely centered on amino acids 26 to 39, contacts the triplex that is one removed from the penton. Importantly, both of these UL25 capsid binding regions are essential for the stable packaging of full-length viral genomes. PMID:21411517

  16. Fast and Accurate Multivariate Gaussian Modeling of Protein Families: Predicting Residue Contacts and Protein-Interaction Partners

    PubMed Central

    Feinauer, Christoph; Procaccini, Andrea; Zecchina, Riccardo; Weigt, Martin; Pagnani, Andrea

    2014-01-01

    In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code. PMID:24663061

  17. Interaction of residue tetracycline hydrochloride in milk with β-galactosidase protein by multi-spectrum methods and molecular docking

    NASA Astrophysics Data System (ADS)

    Gao, Xin; Bi, Hongna; Zuo, Huijun; Jia, Jingjing; Tang, Lin

    2017-08-01

    The purpose of this study was to explore the effect of residue tetracycline hydrochloride (TCH) in milk on molecular structure and activity of β-Gal. Inhibition kinetics assay showed the TCH inhibited β-Gal activity reversibly in a competitive manner. In addition, differences in the activity of β-Gal in the absence and presence of TCH as a function of pH and temperature were found although the optimum pH and temperature of β-Gal remained similar. Fluorescence experiment results showed that TCH effectively quenched the intrinsic fluorescence of β-Gal via static quenching. Thermodynamic parameters delineated the major roles of electrostatic forces played between β-Gal and TCH. Additionally, synchronous fluorescence and circular dichroism spectra (CD spectra) results indicated the secondary structure of β-Gal was changed due to the formation of β-Gal-TCH complexes. The molecular docking further revealed that TCH interacted with some amino acid residues of β-Gal, affecting the active site of the enzyme and thus leading to change in enzyme activity. These alterations in conformation and activity of β-Gal should be taken into consideration while using β-Gal for producing oligosaccharide prebiotics on dairy industries.

  18. Structure-function studies on bacteriorhodopsin. IX. Substitutions of tryptophan residues affect protein-retinal interactions in bacteriorhodopsin

    SciTech Connect

    Mogi, T.; Marti, T.; Khorana, H.G. )

    1989-08-25

    Bacteriorhodopsin contains 8 tryptophan residues distributed across the membrane-embedded helices. To study their possible functions, we have replaced them one at a time by phenylalanine; in addition, Trp-137 and -138 have been replaced by cysteine. The mutants were prepared by cassette mutagenesis of the synthetic bacterio-opsin gene, expression and purification of the mutant apoproteins, renaturation, and chromophore regeneration. The replacement of Trp-10, Trp-12 (helix A), Trp-80 (helix C), and Trp-138 (helix E) by phenylalanine and of Trp-137 and Trp-138 by cysteine did not significantly alter the absorption spectra or affect their proton pumping. However, substitution of the remaining tryptophans by phenylalanine had the following effects. (1) Substitution of Trp-86 (helix C) and Trp-137 gave chromophores blue-shifted by 20 nm and resulted in reduced proton pumping to about 30%. (2) As also reported previously, substitution of Trp-182 and Trp-189 (helix F) caused large blue shifts (70 and 40 nm, respectively) in the chromophore and affected proton pumping. (3) The substitution of Trp-86 and Trp-182 by phenylalanine conferred acid instability on these mutants. The spectral shifts indicate that Trp-86, Trp-182, Trp-189, and possibly Trp-137 interact with retinal. It is proposed that these tryptophans, probably along with Tyr-57 (helix B) and Tyr-185 (helix F), form a retinal binding pocket. We discuss the role of tryptophan residues that are conserved in bacteriorhodopsin, halorhodopsin, and the related family of opsin proteins.

  19. Fast and accurate multivariate Gaussian modeling of protein families: predicting residue contacts and protein-interaction partners.

    PubMed

    Baldassi, Carlo; Zamparo, Marco; Feinauer, Christoph; Procaccini, Andrea; Zecchina, Riccardo; Weigt, Martin; Pagnani, Andrea

    2014-01-01

    In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code.

  20. Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis.

    PubMed

    Anwar, Muhammad Ayaz; Choi, Sangdun

    2017-03-08

    Toll-like receptor 4 (TLR4), a vital innate immune receptor present on cell surfaces, initiates a signaling cascade during danger and bacterial intrusion. TLR4 needs to form a stable hexamer complex, which is necessary to dimerize the cytoplasmic domain. However, D299G and T399I polymorphism may abrogate the stability of the complex, leading to compromised TLR4 signaling. Crystallography provides valuable insights into the structural aspects of the TLR4 ectodomain; however, the dynamic behavior of polymorphic TLR4 is still unclear. Here, we employed molecular dynamics simulations (MDS), as well as principal component and residue network analyses, to decipher the structural aspects and signaling propagation associated with mutations in TLR4. The mutated complexes were less cohesive, displayed local and global variation in the secondary structure, and anomalous decay in rotational correlation function. Principal component analysis indicated that the mutated complexes also exhibited distinct low-frequency motions, which may be correlated to the differential behaviors of these TLR4 variants. Moreover, residue interaction networks (RIN) revealed that the mutated TLR4/myeloid differentiation factor (MD) 2 complex may perpetuate abnormal signaling pathways. Cumulatively, the MDS and RIN analyses elucidated the mutant-specific conformational alterations, which may help in deciphering the mechanism of loss-of-function mutations.

  1. Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis

    PubMed Central

    Anwar, Muhammad Ayaz; Choi, Sangdun

    2017-01-01

    Toll-like receptor 4 (TLR4), a vital innate immune receptor present on cell surfaces, initiates a signaling cascade during danger and bacterial intrusion. TLR4 needs to form a stable hexamer complex, which is necessary to dimerize the cytoplasmic domain. However, D299G and T399I polymorphism may abrogate the stability of the complex, leading to compromised TLR4 signaling. Crystallography provides valuable insights into the structural aspects of the TLR4 ectodomain; however, the dynamic behavior of polymorphic TLR4 is still unclear. Here, we employed molecular dynamics simulations (MDS), as well as principal component and residue network analyses, to decipher the structural aspects and signaling propagation associated with mutations in TLR4. The mutated complexes were less cohesive, displayed local and global variation in the secondary structure, and anomalous decay in rotational correlation function. Principal component analysis indicated that the mutated complexes also exhibited distinct low-frequency motions, which may be correlated to the differential behaviors of these TLR4 variants. Moreover, residue interaction networks (RIN) revealed that the mutated TLR4/myeloid differentiation factor (MD) 2 complex may perpetuate abnormal signaling pathways. Cumulatively, the MDS and RIN analyses elucidated the mutant-specific conformational alterations, which may help in deciphering the mechanism of loss-of-function mutations. PMID:28272553

  2. Interaction between basic residues of Epstein-Barr virus EBNA1 protein and cellular chromatin mediates viral plasmid maintenance.

    PubMed

    Kanda, Teru; Horikoshi, Naoki; Murata, Takayuki; Kawashima, Daisuke; Sugimoto, Atsuko; Narita, Yohei; Kurumizaka, Hitoshi; Tsurumi, Tatsuya

    2013-08-16

    The Epstein-Barr virus (EBV) genome is episomally maintained in latently infected cells. The viral protein EBNA1 is a bridging molecule that tethers EBV episomes to host mitotic chromosomes as well as to interphase chromatin. EBNA1 localizes to cellular chromosomes (chromatin) via its chromosome binding domains (CBDs), which are rich in glycine and arginine residues. However, the molecular mechanism by which the CBDs of EBNA1 attach to cellular chromatin is still under debate. Mutation analyses revealed that stepwise substitution of arginine residues within the CBD1 (amino acids 40-54) and CBD2 (amino acids 328-377) regions with alanines progressively impaired chromosome binding activity of EBNA1. The complete arginine-to-alanine substitutions within the CBD1 and -2 regions abolished the ability of EBNA1 to stably maintain EBV-derived oriP plasmids in dividing cells. Importantly, replacing the same arginines with lysines had minimal effect, if any, on chromosome binding of EBNA1 as well as on its ability to stably maintain oriP plasmids. Furthermore, a glycine-arginine-rich peptide derived from the CBD1 region bound to reconstituted nucleosome core particles in vitro, as did a glycine-lysine rich peptide, whereas a glycine-alanine rich peptide did not. These results support the idea that the chromosome binding of EBNA1 is mediated by electrostatic interactions between the basic amino acids within the CBDs and negatively charged cellular chromatin.

  3. Interaction between Basic Residues of Epstein-Barr Virus EBNA1 Protein and Cellular Chromatin Mediates Viral Plasmid Maintenance*

    PubMed Central

    Kanda, Teru; Horikoshi, Naoki; Murata, Takayuki; Kawashima, Daisuke; Sugimoto, Atsuko; Narita, Yohei; Kurumizaka, Hitoshi; Tsurumi, Tatsuya

    2013-01-01

    The Epstein-Barr virus (EBV) genome is episomally maintained in latently infected cells. The viral protein EBNA1 is a bridging molecule that tethers EBV episomes to host mitotic chromosomes as well as to interphase chromatin. EBNA1 localizes to cellular chromosomes (chromatin) via its chromosome binding domains (CBDs), which are rich in glycine and arginine residues. However, the molecular mechanism by which the CBDs of EBNA1 attach to cellular chromatin is still under debate. Mutation analyses revealed that stepwise substitution of arginine residues within the CBD1 (amino acids 40–54) and CBD2 (amino acids 328–377) regions with alanines progressively impaired chromosome binding activity of EBNA1. The complete arginine-to-alanine substitutions within the CBD1 and -2 regions abolished the ability of EBNA1 to stably maintain EBV-derived oriP plasmids in dividing cells. Importantly, replacing the same arginines with lysines had minimal effect, if any, on chromosome binding of EBNA1 as well as on its ability to stably maintain oriP plasmids. Furthermore, a glycine-arginine-rich peptide derived from the CBD1 region bound to reconstituted nucleosome core particles in vitro, as did a glycine-lysine rich peptide, whereas a glycine-alanine rich peptide did not. These results support the idea that the chromosome binding of EBNA1 is mediated by electrostatic interactions between the basic amino acids within the CBDs and negatively charged cellular chromatin. PMID:23836915

  4. Tyrosine residues 654 and 670 in {beta}-cat enin are crucial in regulation of Met-{beta}-catenin interactions

    SciTech Connect

    Zeng, Gang; Apte, Udayan; Micsenyi, Amanda; Bell, Aaron; Monga, Satdarshan P.S. . E-mail: smonga@pitt.edu

    2006-11-01

    {beta}-catenin, a key component of the canonical Wnt pathway, is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor Met at the membrane. HGF induced Met-{beta}-catenin dissociation and nuclear translocation of {beta}-catenin, which was tyrosine-phosphorylation-dependent. Here, we further investigate the Met-{beta}-catenin interaction by selectively mutating several tyrosine residues, alone or in combination, in {beta}-catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected into rat hepatoma cells, which were treated with HGF. All single or double-mutant-transfected cells continued to show HGF-induced nuclear translocation of FLAG-{beta}-catenin except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of {beta}-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of {beta}-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in {beta}-catenin are crucial in HGF-mediated {beta}-catenin translocation, activation and mitogenesis.

  5. Fermionic Symmetries: Degeneracies when T=0 Two body matrix elements are set equal to zero

    NASA Astrophysics Data System (ADS)

    Zamick, Larry; Robinson, Shadow Jq

    2001-10-01

    the states can be classified by the dual quantum numbers (J_p,J_n). As a counterpoint for angular momenta which are possible for T=3/2 states in ^43Ti or T=2 states in ^44Ti the states cannot be classified by these dual quantum numbers. This is because the wavefunctions for these higher isospin states are basically fractional parentage coefficients, unaffected by what the two body interactions are.

  6. Prediction of FMN-binding residues with three-dimensional probability distributions of interacting atoms on protein surfaces.

    PubMed

    Mahalingam, Rajasekaran; Peng, Hung-Pin; Yang, An-Suei

    2014-02-21

    Flavin mono-nucleotide (FMN) is a cofactor which is involved in many biological reactions. The insights on protein-FMN interactions aid the protein functional annotation and also facilitate in drug design. In this study, we have established a new method, making use of an encoding scheme of the three-dimensional probability density maps that describe the distributions of 40 non-covalent interacting atom types around protein surfaces, to predict FMN-binding sites on protein surfaces. One machine learning model was trained for each of the 30 protein atom types to predict tentative FMN-binding sites on protein structures. The method's capability was evaluated by five-fold cross-validation on a dataset containing 81 non-redundant FMN-binding protein structures and further tested on independent datasets of 30 and 15 non-redundant protein structures respectively. These predictions achieved an accuracy of 0.94, 0.94 and 0.96 with the Matthews correlation coefficient (MCC) of 0.53, 0.53 and 0.65 respectively for the three protein structure sets. The prediction capability is superior to the existing method. This is the first structure-based approach that does not rely on evolutionary information for predicting FMN-interacting residues. The webserver for the prediction is available at http://ismblab.genomics.sinica.edu.tw/.

  7. Relation between the two-body entropy and the relaxation time in supercooled water.

    PubMed

    Gallo, P; Rovere, M

    2015-01-01

    The two-body excess entropy of supercooled water is calculated from the radial distribution functions obtained from computer simulation of the TIP4P model for different densities upon supercooling. This quantity is considered in connection with the relaxation time of the self intermediate scattering function. The relaxation time shows a mode coupling theory (MCT) behavior in the region of mild supercooling and a strong behavior in the deep supercooled region. We find here that the two-body entropy is connected to the relaxation time and shows a logarithmic behavior with an apparent asymptotic divergence at the mode coupling crossover temperature. There is also evidence of a change in behavior of the two-body entropy upon crossing from the fragile (hopping-free) state to the strong (hopping-dominated) state of supercooled water, and the relation that connects the two-body entropy and the relxation time in the MCT region no longer holds.

  8. Gapped two-body hamiltonian whose unique ground state is universal for one-way quantum computation.

    PubMed

    Chen, Xie; Zeng, Bei; Gu, Zheng-Cheng; Yoshida, Beni; Chuang, Isaac L

    2009-06-05

    Many-body entangled quantum states studied in condensed matter physics can be primary resources for quantum information, allowing any quantum computation to be realized using measurements alone, on the state. Such a universal state would be remarkably valuable, if only it were thermodynamically stable and experimentally accessible, by virtue of being the unique ground state of a physically reasonable Hamiltonian made of two-body, nearest-neighbor interactions. We introduce such a state, composed of six-state particles on a hexagonal lattice, and describe a general method for analyzing its properties based on its projected entangled pair state representation.

  9. Two-body gravitational spin-orbit interaction at linear order in the mass ratio

    NASA Astrophysics Data System (ADS)

    Bini, Donato; Damour, Thibault

    2014-07-01

    We analytically compute, to linear order in the mass ratio, the "geodetic" spin-precession frequency of a small spinning body orbiting a large (nonspinning) body to the eight-and-a-half post-Newtonian order, thereby extending previous analytical knowledge which was limited to the third post-Newtonian level. These results are obtained applying analytical gravitational self-force theory to the first-derivative level generalization of Detweiler's gauge-invariant redshift variable. We compare our analytic results with strong-field numerical data recently obtained by Dolan et al. [Phys. Rev. D 89, 064011 (2014)]. Our new, high-post-Newtonian-order results capture the strong-field features exhibited by the numerical data. We argue that the spin precession will diverge as ≈-0.14/(1-3y) as the light ring is approached. We transcribe our kinematical spin-precession results into a corresponding improved analytic knowledge of one of the two (gauge-invariant) effective gyrogravitomagnetic ratios characterizing spin-orbit couplings within the effective-one-body formalism. We provide simple, accurate analytic fits both for spin precession and the effective gyrogravitomagnetic ratio. The latter fit predicts that the linear-in-mass-ratio correction to the gyrogravitomagnetic ratio changes sign before reaching the light ring. This strong-field prediction might be important for improving the analytic modeling of coalescing spinning binaries.

  10. Systematics of the release of residual nuclei from relativistic nucleus-nucleus interactions

    NASA Technical Reports Server (NTRS)

    Binns, W. R.; Israel, M. H.; Klarmann, J.; Garrard, T. L.; Kertzmann, M. P.

    1987-01-01

    Relativistic nuclei of krypton, xenon, holmium, and gold, accelerated in a partially stripped state to a maximum rigidity of about 5.6 GeV, interacting with targets of aluminum, carbon, and polyethylene are examined. For each projectile and target combination, determinations are made for the total and partial charge changing cross sections for the production of lighter fragments. From these measurements, a new representation of the dependence of the total charge changing cross sections on beam and target charge is developed. Simple representations of the variation of the partial cross sections were identified with the charge of the produced fragments and shown to be dependent on the charge and energy of the beam. The fission of gold nuclei at high energies in these various targets has also been studied.

  11. Sensitivity of P-glycoprotein tryptophan residues to benzodiazepines and ATP interaction.

    PubMed

    Lima, Sofia A C; Cordeiro-da-Silva, Anabela; de Castro, Baltazar; Gameiro, Paula

    2007-01-01

    Plasma membrane P-glycoprotein is a member of the ATP-binding cassette family of membrane transporters. In the present study tryptophan intrinsic fluorescence was used to understand the P-glycoprotein response to three benzodiazepines (bromazepam, chlordiazepoxide and flurazepam) in the presence and absence of ATP. Fluorescence emission spectra showed a red shift on the maximal emission wavelength upon interaction of P-glycoprotein with all benzodiazepines. Benzodiazepine association with nucleotide-bound P-glycoprotein also showed this trend and the quenching profile was attributed to a sphere-of-action model, for static fluorescence. Furthermore, quenching data of benzodiazepine-bound P-glycoprotein with ATP were concentration dependent and saturable, indicating that nucleotide binds to P-glycoprotein whether drug is present or not. These results seems in agreement with the proposal of the ATP-switch model by Higgins and Linton, where substrate binding to the transporters initiates the transport cycle by increasing the ATP binding affinity.

  12. Functional assessment of three Rem residues identified as critical for interactions with Ca(2+) channel β subunits.

    PubMed

    Beqollari, Donald; Romberg, Christin F; Filipova, Dilyana; Papadopoulos, Symeon; Bannister, Roger A

    2015-11-01

    Members of the Rem, Rem2, Rad, Gem/Kir (RGK) family of small GTP-binding proteins inhibit high-voltage-activated (HVA) Ca(2+) channels through interactions with both the principal α1 and the auxiliary β subunits of the channel complex. Three highly conserved residues of Rem (R200, L227, and H229) have been shown in vitro to be critical for interactions with β subunits. However, the functional significance of these residues is not known. To investigate the contributions of R200, L227, and H229 to β subunit-mediated RGK protein-dependent inhibition of HVA channels, we introduced alanine substitutions into all three positions of Venus fluorescent protein-tagged Rem (V-Rem AAA) and made three other V-Rem constructs with an alanine introduced at only one position (V-Rem R200A, V-Rem L227A, and V-Rem H229A). Confocal imaging and immunoblotting demonstrated that each Venus-Rem mutant construct had comparable expression levels to Venus-wild-type Rem when heterologously expressed in tsA201 cells. In electrophysiological experiments, V-Rem AAA failed to inhibit N-type Ca(2+) currents in tsA201 cells coexpressing CaV2.2 α1B, β3, and α2δ-1 channel subunits. The V-Rem L227A single mutant also failed to reduce N-type currents conducted by coexpressed CaV2.2 channels, a finding consistent with the previous observation that a leucine at position 227 is critical for Rem-β interactions. Rem-dependent inhibition of CaV2.2 channels was impaired to a much lesser extent by the R200A substitution. In contrast to the earlier work demonstrating that Rem H229A was unable to interact with β3 subunits in vitro, V-Rem H229A produced nearly complete inhibition of CaV2.2-mediated currents.

  13. Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication

    PubMed Central

    Stetz, Gabrielle; Verkhivker, Gennady M.

    2017-01-01

    Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we

  14. Tyr-199 and charged residues of pharaonis Phoborhodopsin are important for the interaction with its transducer.

    PubMed Central

    Sudo, Yuki; Iwamoto, Masayuki; Shimono, Kazumi; Kamo, Naoki

    2002-01-01

    pharaonis Phoborhodopsin (ppR; also pharaonis sensory rhodopsin II, psRII) is a retinal protein in Natronobacterium pharaonis and is a receptor of negative phototaxis. It forms a complex with its transducer, pHtrII, in membranes and transmits light signals by protein-protein interaction. Tyr-199 is conserved completely in phoborhodopsins among a variety of archaea, but it is replaced by Val (for bacteriorhodopsin) and Phe (for sensory rhodopsin I). Previously, we (Sudo, Y., M. Iwamoto, K. Shimono, and N. Kamo, submitted for publication) showed that analysis of flash-photolysis data of a complex between D75N and the truncated pHtrII (t-Htr) give a good estimate of the dissociation constant K(D) in the dark. To investigate the importance of Tyr-199, K(D) of double mutants of D75N/Y199F or D75N/Y199V with t-Htr was estimated by flash-photolysis and was approximately 10-fold larger than that of D75N, showing the significant contribution of Tyr-199 to binding. The K(D) of the D75N/t-Htr complex increased with decreasing pH, and the data fitted well with the Henderson-Hasselbach equation with a single pK(a) of 3.86 +/- 0.02. This suggests that certain deprotonated carboxyls at the surface of the transducer (possibly Asp-102, Asp-104, and Asp-106) are needed for the binding. PMID:12080131

  15. Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions

    PubMed Central

    Chaudhari, Rajan; Heim, Andrew J.

    2017-01-01

    Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of “modeling first, refinement next”. In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of “refined restraints first, modeling next”, provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins. PMID:25503850

  16. Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions

    NASA Astrophysics Data System (ADS)

    Chaudhari, Rajan; Heim, Andrew J.; Li, Zhijun

    2015-05-01

    Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.

  17. Improving homology modeling of G-protein coupled receptors through multiple-template derived conserved inter-residue interactions.

    PubMed

    Chaudhari, Rajan; Heim, Andrew J; Li, Zhijun

    2015-05-01

    Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy of "modeling first, refinement next". In the present work, we developed an alternative modeling approach through the novel application of available multiple templates. First, conserved inter-residue interactions are derived from each additional template through conservation analysis of each template-target pairwise alignment. Then, these interactions are converted into distance restraints and incorporated in the homology modeling process. This approach was applied to modeling of the human β2 adrenergic receptor using the bovin rhodopsin and the human protease-activated receptor 1 as templates and improved model quality was demonstrated compared to the homology model generated by standard single-template and multiple-template methods. This method of "refined restraints first, modeling next", provides a fast and complementary way to the current modeling approaches. It allows rational identification and implementation of additional conserved distance restraints extracted from multiple templates and/or experimental data, and has the potential to be applicable to modeling of all helical transmembrane proteins.

  18. Developing a high-quality scoring function for membrane protein structures based on specific inter-residue interactions

    NASA Astrophysics Data System (ADS)

    Heim, Andrew J.; Li, Zhijun

    2012-03-01

    Membrane proteins are of particular biological and pharmaceutical importance, and computational modeling and structure prediction approaches play an important role in studies of membrane proteins. Developing an accurate model quality assessment program is of significance to the structure prediction of membrane proteins. Few such programs are proposed that can be applied to a broad range of membrane protein classes and perform with high accuracy. We developed a new model scoring function Interaction-based Quality assessment (IQ), based on the analysis of four types of inter-residue interactions within the transmembrane domains of helical membrane proteins. This function was tested using three high-quality model sets: all 206 models of GPCR Dock 2008, all 284 models of GPCR Dock 2010, and all 92 helical membrane protein models of the HOMEP set. For all three sets, the scoring function can select the native structures among all of the models with the success rates of 93, 85, and 100% respectively. For comparison, these three model sets were also adopted for a recently published model assessment program for membrane protein structures, ProQM, which gave the success rates of 85, 79, and 92% separately. These results suggested that IQ outperforms ProQM when only the transmembrane regions of the models are considered. This scoring function should be useful for the computational modeling of membrane proteins.

  19. Spring Chinook Salmon Interactions Indices and Residual/Precocial Monitoring in the Upper Yakima Basin, 1998 Annual Report.

    SciTech Connect

    James, Brenda B.; Pearsons, Todd N.; McMichael, Geoffrey A.

    1999-12-01

    Select ecological interactions and spring chinook salmon residual/precocial abundance were monitored in 1998 as part of the Yakima/Klickitat Fisheries Project's supplementation monitoring program. Monitoring these variables is part of an effort to help evaluate the factors that contribute to, or limit supplementation success. The ecological interactions that were monitored were prey consumption, competition for food, and competition for space. The abundance of spring chinook salmon life-history forms that have the potential to be influenced by supplementation and that have important ecological and genetic roles were monitored (residuals and precocials). Residual spring chinook salmon do not migrate to the ocean during the normal emigration period and continue to rear in freshwater. Precocials are those salmon that precocially mature in freshwater. The purpose of sampling during 1998 was to collect baseline data one year prior to the release of hatchery spring chinook salmon which occurred during the spring of 1999. All sampling that the authors report on here was conducted in upper Yakima River during summer and fall 1998. The stomach fullness of juvenile spring chinook salmon during the summer and fall averaged 12%. The food competition index suggested that mountain whitefish (0.59), rainbow trout (0.55), and redside shiner (0.55) were competing for food with spring chinook salmon. The space competition index suggested that rainbow trout (0.31) and redside shiner (0.39) were competing for space with spring chinook salmon but mountain whitefish (0.05) were not. Age-0 spring chinook salmon selected a fairly narrow range of microhabitat parameters in the summer and fall relative to what was available. Mean focal depths and velocities for age 0 spring chinook salmon during the summer were 0.5 m {+-} 0.2 m and 0.26 m/s {+-} 0.19 m/s, and during the fall 0.5 m {+-} 0.2 m and 0.24 m/s {+-} 0.18 m/s. Among potential competitors, age 1+ rainbow trout exhibited the greatest

  20. [Determination of melamine residue in raw milk and dairy products using hydrophilic interaction chromatography-electrospray ionization tandem mass spectrometry].

    PubMed

    Yan, Lijuan; Wu, Min; Zhang, Zhigang; Zhou, Yu; Lin, Liyi; Fang, Enhua; Xu, Dunming; Chen, Luping

    2008-11-01

    A method for the determination of melamine residue in raw milk and dairy products was developed using hydrophilic interaction chromatography-electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS). The melamine residue in the test sample was extracted with 1% trichloroacetic acid-acetonitrile (1 : 1, v/v) solution. The homogenate was centrifuged and the supernatant was collected. The extract was cleaned up using a mixed-mode cation exchange (MCX) solid-phase extraction cartridge and then concentrated, and analyzed by HILIC-ESI-MS/MS. The gradient chromatographic separation was performed using a hydrophilic silica column (250 mm x 4.6 mm, 5 microm) with 10 mmol/L ammonium acetate buffer (pH 3.0) and acetonitrile as the mobile phases. Due to its hydrophilic property, melamine was well retained on the column and seperated from other compounds. It effectively reduced matrix effect. A triple quadruple mass spectrometer equipped with an electrospray ionization source was employed for the qualitative and quantitative measurement of melamine. The melamine was quantified using the fragments produced from the protonated melamine ion through multiple reaction monitoring (MRM) in positive ion mode. Two MRM transitions from the protonated melamine ion (m/z 127 --> 85 and m/z 127 --> 68) were monitored. The average recoveries were between 76.3% and 98.7% in the spiked range of 0.5 to 10 mg/kg in raw milk and dairy products, and the relative standard deviations were less than 6.8%. The linear range was from 0.05 to 10.0 mg/L. The limit of quantification (S/N > 10) was 0.05 mg/kg. The method is highly selective and sensitive for the measurements of melamine and adequate for the analysis of melamine in raw milk and dairy products.

  1. Effects of Ca/sup 2 +/ and subunit interactions on surface accessibility of cysteine residues in cardiac troponin

    SciTech Connect

    Ingraham, R.H.; Hodges, R.S.

    1988-08-09

    Rabbit and bovine cardiac troponin (Tn) subunits and complexes were labeled with iodo(/sup 14/C)acetamide in the presence and absence of Ca/sup 2 +/ to determine the effects of tertiary and quaternary structure on exposure of Cys SH groups. This procedure serves both to map region of subunit interaction and the effects of Ca/sup 2 +/-induced conformational change and to indicate which Cys residues should be useful attachment sites for spectroscopic or cross-linking probes. After being labeled, Tn subunits were purified by using reversed-phase HPLC and subjected to tryptic cleavage with or without prior citraconylation. Cys-containing fragments were isolated by RP-HPLC, and the percent labeling was determined. Cys-75 and -92 of TnI were completely accessible to iodoacetamide both when TnI was labeled alone or when in the TnC-TnI complex. Both residues were largely inaccessible when Tn or the TnI-TnT complex was labeled, suggesting burial in the TnI-TnT interface. In contrast, the Cys from the N-terminal region of bovine TnT was stoichiometrically labeled when TnT was labeled alone, in native Tn or in a troponin-tropomyosin complex. Cys-35 and -84 of TnC are located in the nonfunctional Ca/sup 2 +/ binding loop I of cardiac TnC and helix D, respectively. For TnC alone, the percent labelings of Cys-35 and -84 were 11% and 26%, respectively (minus Ca/sup 2 +/), and 16% and 63%, respectively (plus Ca/sup 2 +/). For TnC labeled within Tn, the percent labelings of Cys-35 and -84 were 20% and 52%, respectively (minus Ca/sup 2 +/), and 20% and 78%, respectively (plus Ca/sup 2 +/). The Ca/sup 2 +/-induced exposure of these residues, especially Cys-84, supports the Ca/sup 2 +/-activated model of turkey skeletal TnC derived from crystallographic data.

  2. Validation of Proposed Metrics for Two-Body Abrasion Scratch Test Analysis Standards

    NASA Technical Reports Server (NTRS)

    Kobrick, Ryan L.; Klaus, David M.; Street, Kenneth W., Jr.

    2011-01-01

    The objective of this work was to evaluate a set of standardized metrics proposed for characterizing a surface that has been scratched from a two-body abrasion test. This is achieved by defining a new abrasion region termed Zone of Interaction (ZOI). The ZOI describes the full surface profile of all peaks and valleys, rather than just measuring a scratch width as currently defined by the ASTM G 171 Standard. The ZOI has been found to be at least twice the size of a standard width measurement, in some cases considerably greater, indicating that at least half of the disturbed surface area would be neglected without this insight. The ZOI is used to calculate a more robust data set of volume measurements that can be used to computationally reconstruct a resultant profile for detailed analysis. Documenting additional changes to various surface roughness parameters also allows key material attributes of importance to ultimate design applications to be quantified, such as depth of penetration and final abraded surface roughness. Data are presented to show that different combinations of scratch tips and abraded materials can actually yield the same scratch width, but result in different volume displacement or removal measurements and therefore, the ZOI method is more discriminating than the ASTM method scratch width. Furthermore, by investigating the use of custom scratch tips for our specific needs, the usefulness of having an abrasion metric that can measure the displaced volume in this standardized manner, and not just by scratch width alone, is reinforced. This benefit is made apparent when a tip creates an intricate contour having multiple peaks and valleys within a single scratch. This work lays the foundation for updating scratch measurement standards to improve modeling and characterization of three-body abrasion test results.

  3. Importance of the character and configuration of residues B24, B25, and B26 in insulin-receptor interactions

    SciTech Connect

    Mirmira, R.G.; Nakagawa, S.H.; Tager, H.S. )

    1991-01-25

    By use of isolated canine hepatocytes and insulin analogs prepared by trypsin-catalyzed semisynthesis, we have investigated the importance of the aromatic triplet PheB24-PheB25-TyrB26 of the COOH-terminal B-chain domain of insulin in directing the affinity of insulin-receptor interactions. Analysis of the receptor binding potencies of analogs bearing transpositions or replacements (by Tyr, D-Tyr or their corresponding 3,5-diiodo derivatives) in this region demonstrates a wide divergence in the acceptance both of configurational change (with (D-TyrB24,PheB26)insulin and (D-TyrB25,PheB26)insulin exhibiting 160 and 0.1% of the receptor binding potency of insulin, respectively) and of detailed side chain structure (with (TyrB24,PheB26)insulin and (TyrB25,PheB26)insulin exhibiting 2 and 80% of the receptor binding potency of insulin, respectively). Additional experiments addressed the solvent accessibilities of the 4 tyrosine residues of insulin and the insulin analogs at selected peptide concentrations by use of analytical radioiodination. Whereas two analogs ((TyrB25,PheB26)insulin and (D-TyrB24,PheB26)insulin) were found to undergo self aggregation, no strict correlation was found between the ability of an analog to aggregate and its potency for interaction with the insulin receptor. Related findings are discussed in terms of the interplay between side chain and main chain structure in the COOH-terminal domain of the insulin B-chain and the structural attributes of insulin that determine the affinity of insulin-receptor interactions.

  4. Conformational mapping and energetics of saccharide-aromatic residue interactions: implications for the discrimination of anomers and epimers and in protein engineering.

    PubMed

    Kumari, Manju; Sunoj, Raghavan B; Balaji, Petety V

    2012-06-07

    Aromatic residues play a key role in saccharide-binding sites. Experimental studies have given an estimate of the energetics of saccharide-aromatic residue interactions. In this study, dependence of the energetics on the mutual position-orientation (PO) of saccharide and aromatic residue has been investigated by geometry optimization of a very large number (164) of complexes at MP2/6-31G(d,p) level of theory. The complexes are of Tyr and Phe analogs with α/β-D-Glc, β-D-Gal, α-D-Man and α/β-L-Fuc. A number of iso-energy POs are found for the complexes of all six saccharides. Stacking and non-stacking modes of binding are found to be of comparable strengths. In general, complexes of p-OHTol are stronger than those of Tol, and those dominated by OH···O interactions are more stable than ones dominated by CH···π interactions. The strengths of OH···O/π interactions, but not those of CH···π, show large variations. Even though an aromatic residue has a large variety of POs to interact with a saccharide, distinct preferences are found due to anomeric and epimeric differences. An aromatic residue can interact from either the a- or b-face of Glc, but only through the b-face with Gal, its C4-epimer. In contrast, stacking interaction with Man (C2-epimer of Glc) requires the participation of the -CH(2)OH group and free rotation of this group, as is observed in solution, precludes all modes of stacking interactions. It is also found that an aromatic residue can be strategically placed either to discriminate or to accommodate (i) anomers of Glc and of Fuc and (ii) Gal/Fuc. Thus, analysis of the optimized geometries of by far the largest number of complexes, and with six different saccharides, at this level of theory has given insights into how Nature cleverly uses aromatic residues to fine tune saccharide specificities of proteins. These are of immense utility for protein engineering and protein design studies.

  5. Analytical treatment of the two-body problem with slowly varying mass

    NASA Astrophysics Data System (ADS)

    Rahoma, W. A.; Abd El-Salam, F. A.; Ahmed, M. K.

    2009-12-01

    The present work is concerned with the two-body problem with varying mass in case of isotropic mass loss from both components of the binary systems. The law of mass variation used gives rise to a perturbed Keplerian problem depending on two small parameters. The problem is treated analytically in the Hamiltonian frame-work and the equations of motion are integrated using the Lie series developed and applied, separately by Delva (1984) and Hanslmeier (1984). A second order theory of the two bodies eject mass is constructed, returning the terms of the rate of change of mass up to second order in the small parameters of the problem.

  6. Analytical expressions for partial wave two-body Coulomb transition matrices at ground-state energy

    NASA Astrophysics Data System (ADS)

    Kharchenko, V. F.

    2016-11-01

    Leaning upon the Fock method of the stereographic projection of the three-dimensional momentum space onto the four-dimensional unit sphere the possibility of the analytical solving of the Lippmann-Schwinger integral equation for the partial wave two-body Coulomb transition matrix at the ground bound state energy has been studied. In this case new expressions for the partial p-, d- and f-wave two-body Coulomb transition matrices have been obtained in the simple analytical form. The developed approach can also be extended to determine analytically the partial wave Coulomb transition matrices at the energies of excited bound states.

  7. Neutral weak-current two-body contributions in inclusive scattering from {sup 12}C

    SciTech Connect

    Lovato, Alessandro; Gandolfi, Stefano; Carlson, Joseph; Pieper, S. C.; Schiavilla, Rocco

    2014-05-01

    An {\\it ab initio} calculation of the sum rules of the neutral weak response functions in $^{12}$C is reported, based on a realistic Hamiltonian, including two- and three-nucleon potentials, and on realistic currents, consisting of one- and two-body terms. We find that the sum rules of the response functions associated with the longitudinal and transverse components of the (space-like) neutral current are largest and that a significant portion ($\\simeq 30$\\%) of the calculated strength is due to two-body terms. This fact may have implications for the MiniBooNE and other neutrino quasi-elastic scattering data on nuclei.

  8. Interaction of serum amyloid A with human cystatin C--assessment of amino acid residues crucial for hCC-SAA formation (part II).

    PubMed

    Spodzieja, Marta; Rafalik, Monika; Szymańska, Aneta; Kołodziejczyk, Aleksandra S; Czaplewska, Paulina

    2013-09-01

    Secondary amyloid A (AA) amyloidosis is an important complication of some chronic inflammatory diseases, primarily rheumatoid arthritis (RA). It is a serious, potentially life-threatening disorder caused by the deposition of AA fibrils, which are derived from the circulatory, acute-phase-reactant, serum amyloid A protein (SAA). Recently, a specific interaction between SAA and the ubiquitous inhibitor of cysteine proteases--human cystatin C (hCC)--has been proved. Using a combination of selective proteolytic excision and high-resolution mass spectrometry, the binding sites in the SAA and hCC sequences were assessed as SAA(86-104) and hCC(96-102), respectively. Here, we report further details concerning the hCC-SAA interaction. With the use of affinity tests and florescent ELISA-like assays, the amino acid residues crucial for the protein interaction were determined. It was shown that all amino acid residues in the SAA sequence, essential for the formation of the protein complex, are basic ones, which suggests an electrostatic interaction character. The idea is corroborated by the fact that the most important residues in the hCC sequence are Ser-98 and Tyr-102; these residues are able to form hydrogen bonds via their hydroxyl groups. The molecular details of hCC-SAA complex formation might be helpful for the design of new compounds modulating the biological role of both proteins. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Low-energy structure studies of odd-odd deformed nuclei and the coriolis and residual interactions

    SciTech Connect

    Dewberry, R.A.

    1980-08-01

    The nuclear level structure of /sup 176/Lu, /sup 170/Tm, /sup 166/Ho, and /sup 160/Tb have been studied by means of the /sup 177/Hf(t,..cap alpha..)/sup 176/Lu, /sup 171/Yb(t,..cap alpha..)/sup 170/Tm, /sup 167/Er(t,..cap alpha..)/sup 166/Ho, and /sup 161/Dy(t,..cap alpha..)/sup 160/Tb reactions and with the use of previously published (d,p) spectroscopy and gamma transitions from the (n,..gamma..) reactions. The (t,..cap alpha..) reactions have been performed and analyzed with 17 MeV tritons and the Los Alamos Q3D spectrometer. Eighty-one new rotational states in excited proton configurations or vibrational excited states are proposed. An independent parameterization of the Coriolis interaction is presented, which leads to satisfactory results in reproducing experimental single-particle transfer reaction cross-sections by theoretical calculations. The anomalous population of the excited neutron configurations (404 reduces to -624 up arrow) in /sup 176/Lu and (411 reduces to +- 512 up arrow) in /sup 170/Tm, and the anomalously low (t,..cap alpha..) cross-sections of the (411 up arrow +- 633 up arrow) configuration in /sup 166/Ho are observed. Qualitative explanation of the anomalies is presented in terms of the mixing of states which satisfy the requirement delta/sub I'/,/sub I/delta/sub K'/,/sub K/. Off-diagonal H/sub INT/ matrix elements are calculated, which show that the residual interaction cannot be used to account for the magnitude of the cross-sections observed.

  10. Identification of residues crucial for the interaction between human neuroglobin and the α-subunit of heterotrimeric Gi protein

    PubMed Central

    Takahashi, Nozomu; Wakasugi, Keisuke

    2016-01-01

    Mammalian neuroglobin (Ngb) protects neuronal cells under conditions of oxidative stress. We previously showed that human Ngb acts as a guanine nucleotide dissociation inhibitor (GDI) for the α-subunits of heterotrimeric Gi/o proteins and inhibits the decrease in cAMP concentration, leading to protection against cell death. In the present study, we used an eukaryotic expression vector driving high-level expression of human wild-type Ngb or Ngb mutants that either exhibit or lack GDI activities in human cells. We demonstrate that the GDI activity of human Ngb is tightly correlated with its neuroprotective activity. We further demonstrate that Glu53, Glu60, and Glu118 of human Ngb are crucial for both the neuroprotective activity and interaction with Gαi1. Moreover, we show that Lys46, Lys70, Arg208, Lys209, and Lys210 residues of Gαi1 are important for binding to human Ngb. We propose a molecular docking model of the complex between human Ngb and Gαi1. PMID:27109834

  11. The Role of the Lys628 (192) Residue of the Complement Protease, C1s, in Interacting with Peptide and Protein Substrates

    PubMed Central

    Wijeyewickrema, Lakshmi Carmel; Duncan, Renee Charlene; Pike, Robert Neil

    2014-01-01

    The C1s protease of the classical complement pathway propagates the initial activation of this pathway of the system by cleaving and thereby activating the C4 and C2 complement components. This facilitates the formation of the classical pathway C3 convertase (C4bC2a). C1s has a Lys residue located at position 628 (192 in chymotrypsin numbering) of the SP domain that has the potential to partially occlude the S2–S2′ positions of the active site. The 192 residue of serine proteases generally plays an important role in interactions with substrates. We therefore investigated the role of Lys628 (192) in interactions with C4 by altering the Lys residue to either a Gln (found in many other serine proteases) or an Ala residue. The mutant enzymes had altered specificity profiles for a combinatorial peptide substrate library, suggesting that this residue does influence the active site specificity of the protease. Generally, the K628Q mutant had greater activity than wild type enzyme against peptide substrates, while the K628A residue had lowered activity, although this was not always the case. Against peptide substrates containing physiological substrate sequences, the K628Q mutant once again had generally higher activity, but the activity of the wild type and mutant enzymes against a C4 P4–P4′ substrate were similar. Interestingly, alteration of the K628 residue in C1s had a marked effect on the cleavage of C4, reducing cleavage efficiency for both mutants about fivefold. This indicates that this residue plays a different role in cleaving protein versus peptide substrates and that the Lys residue found in the wild type enzyme plays an important role in interacting with the C4 substrate. Understanding the basis of the interaction between C1s and its physiological substrates is likely to lead to insights that can be used to design efficient inhibitors of the enzyme for use in treating diseases caused by inflammation as result of over-activity of the classical

  12. Towards numerically robust multireference theories: The driven similarity renormalization group truncated to one- and two-body operators

    NASA Astrophysics Data System (ADS)

    Li, Chenyang; Evangelista, Francesco A.

    2016-04-01

    The first nonperturbative version of the multireference driven similarity renormalization group (MR-DSRG) theory [C. Li and F. A. Evangelista, J. Chem. Theory Comput. 11, 2097 (2015)] is introduced. The renormalization group structure of the MR-DSRG equations ensures numerical robustness and avoidance of the intruder-state problem, while the connected nature of the amplitude and energy equations guarantees size consistency and extensivity. We approximate the MR-DSRG equations by keeping only one- and two-body operators and using a linearized recursive commutator approximation of the Baker-Campbell-Hausdorff expansion [T. Yanai and G. K.-L. Chan, J. Chem. Phys. 124, 194106 (2006)]. The resulting linearized MR-DSRG scheme with one- and two-body operators [MR-LDSRG(2)] contains only 39 terms and scales as O ( N 2 NP 2 NH 2 ) where NH, NP, and N correspond to the number of hole, particle, and total orbitals, respectively. Benchmark MR-LDSRG(2) computations on the hydrogen fluoride and molecular nitrogen binding curves and the singlet-triplet splitting of p-benzyne yield results comparable in accuracy to those from multireference configuration interaction, Mukherjee multireference coupled cluster theory, and internally contracted multireference coupled cluster theory.

  13. Towards numerically robust multireference theories: The driven similarity renormalization group truncated to one- and two-body operators.

    PubMed

    Li, Chenyang; Evangelista, Francesco A

    2016-04-28

    The first nonperturbative version of the multireference driven similarity renormalization group (MR-DSRG) theory [C. Li and F. A. Evangelista, J. Chem. Theory Comput. 11, 2097 (2015)] is introduced. The renormalization group structure of the MR-DSRG equations ensures numerical robustness and avoidance of the intruder-state problem, while the connected nature of the amplitude and energy equations guarantees size consistency and extensivity. We approximate the MR-DSRG equations by keeping only one- and two-body operators and using a linearized recursive commutator approximation of the Baker-Campbell-Hausdorff expansion [T. Yanai and G. K.-L. Chan, J. Chem. Phys. 124, 194106 (2006)]. The resulting linearized MR-DSRG scheme with one- and two-body operators [MR-LDSRG(2)] contains only 39 terms and scales as O(N(2)NP (2)NH (2)) where NH, NP, and N correspond to the number of hole, particle, and total orbitals, respectively. Benchmark MR-LDSRG(2) computations on the hydrogen fluoride and molecular nitrogen binding curves and the singlet-triplet splitting of p-benzyne yield results comparable in accuracy to those from multireference configuration interaction, Mukherjee multireference coupled cluster theory, and internally contracted multireference coupled cluster theory.

  14. Two-quasineutron states in {sup 248}{sub 98}Cf and {sup 250}{sub 98}Cf and the neutron-neutron residual interactions.

    SciTech Connect

    Katori, K.; Ahmad, I.; Friedman, A. M.; Physics; Osaka Univ.

    2008-07-01

    Two-quasineutron states in {sup 248}Cf and {sup 250}Cf were investigated by single-neutron transfer reactions, {sup 249}Cf(d,t){sup 248}Cf and {sup 249}Cf(d,p){sup 250}Cf. The majority of levels observed were assigned to 12 bands in {sup 248}Cf and six bands in {sup 250}Cf, constructed from the single-particle states in neighboring Cf nuclei. The effective two-body interactions between two odd neutrons coupled outside a deformed core were deduced from the differences in the energies of the bandheads formed by the parallel and antiparallel coupling of the intrinsic spins of the two single-particle states.

  15. Two-quasineutron states in {sub 98}{sup 248}Cf and {sub 98}{sup 250}Cf and the neutron-neutron residual interactions

    SciTech Connect

    Katori, K.; Ahmad, I.; Friedman, A. M.

    2008-07-15

    Two-quasineutron states in {sup 248}Cf and {sup 250}Cf were investigated by single-neutron transfer reactions, {sup 249}Cf(d,t){sup 248}Cf and {sup 249}Cf(d,p){sup 250}Cf. The majority of levels observed were assigned to 12 bands in {sup 248}Cf and six bands in {sup 250}Cf, constructed from the single-particle states in neighboring Cf nuclei. The effective two-body interactions between two odd neutrons coupled outside a deformed core were deduced from the differences in the energies of the bandheads formed by the parallel and antiparallel coupling of the intrinsic spins of the two single-particle states.

  16. [Effect of mutations and modifications of amino acid residues on zinc-induced interaction of the metal-binding domain of β-amyloid with DNA].

    PubMed

    Khmeleva, S A; Mezentsev, Y V; Kozin, S A; Mitkevich, V A; Medvedev, A E; Ivanov, A S; Bodoev, N V; Makarov, A A; Radko, S P

    2015-01-01

    Interaction of intranuclear β-amyloid with DNA is considered to be a plausible mechanism of Alzheimer's disease pathogenesis. The interaction of single- and double-stranded DNA with synthetic peptides was analyzed using surface plasmon resonance. The peptides represent the metal-binding domain of β-amyloid (amino acids 1-16) and its variants with chemical modifications and point substitutions of amino acid residues which are associated with enhanced neurotoxicity of β-amyloid in cell tests. It has been shown that the presence of zinc ions is necessary for the interaction of the peptides with DNA in solution. H6R substitution has remarkably reduced the ability of domain 1-16 to bind DNA. This is in accordance with the supposition that the coordination of a zinc ion by amino acid residues His6, Glu11, His13, and His14 of the β-amyloid metal-binding domain results in the occurrence of an anion-binding site responsible for the interaction of the domain with DNA. Zinc-induced dimerization and oligomerization of domain 1-16 associated with phosphorylation of Ser8 and the presence of unblocked amino- and carboxy-terminal groups have resulted in a decrease of peptide concentrations required for detection of the peptide-DNA interaction. The presence of multiple anion-binding sites on the dimers and oligomers is responsible for the enhancement of the peptide-DNA interaction. A substitution of the negatively charged residue Asp7 for the neutral residue Asn in close proximity to the anion-binding site of the domain 1-16 of Aβ facilitates the electrostatic interaction between this site and phosphates of a polynucleotide chain, which enhances zinc-induced binding to DNA.

  17. Aromatic residues in the C-terminal helix of human apoC-I mediate phospholipid interactions and particle morphology.

    PubMed

    James, Patrick F; Dogovski, Con; Dobson, Renwick C J; Bailey, Michael F; Goldie, Kenneth N; Karas, John A; Scanlon, Denis B; O'Hair, Richard A J; Perugini, Matthew A

    2009-07-01

    Human apolipoprotein C-I (apoC-I) is an exchangeable apolipoprotein that binds to lipoprotein particles in vivo. In this study, we employed a LC-MS/MS assay to demonstrate that residues 38-51 of apoC-I are significantly protected from proteolysis in the presence of 1,2-dimyristoyl-3-sn-glycero-phosphocholine (DMPC). This suggests that the key lipid-binding determinants of apoC-I are located in the C-terminal region, which includes F42 and F46. To test this, we generated site-directed mutants substituting F42 and F46 for glycine or alanine. In contrast to wild-type apoC-I (WT), which binds DMPC vesicles with an apparent Kd [Kd(app)] of 0.89 microM, apoC-I(F42A) and apoC-I(F46A) possess 2-fold weaker affinities for DMPC with Kd(app) of 1.52 microM and 1.58 microM, respectively. However, apoC-I(F46G), apoC-I(F42A/F46A), apoC-I(F42G), and apoC-I(F42G/F46G) bind significantly weaker to DMPC with Kd(app) of 2.24 microM, 3.07 microM, 4.24 microM, and 10.1 microM, respectively. Sedimentation velocity studies subsequently show that the protein/DMPC complexes formed by these apoC-I mutants sediment at 6.5S, 6.7S, 6.5S, and 8.0S, respectively. This is compared with 5.0S for WT apoC-I, suggesting the shape of the particles was different. Transmission electron microscopy confirmed this assertion, demonstrating that WT forms discoidal complexes with a length-to-width ratio of 2.57, compared with 1.92, 2.01, 2.16, and 1.75 for apoC-I(F42G), apoC-I(F46G), apoC-I(F42A/F46A), and apoC-I(F42G/F46G), respectively. Our study demonstrates that the C-terminal amphipathic alpha-helix of human apoC-I contains the major lipid-binding determinants, including important aromatic residues F42 and F46, which we show play a critical role in stabilizing the structure of apoC-I, mediating phospholipid interactions, and promoting discoidal particle morphology.

  18. Aromatic residues in the C-terminal helix of human apoC-I mediate phospholipid interactions and particle morphologys⃞

    PubMed Central

    James, Patrick F.; Dogovski, Con; Dobson, Renwick C. J.; Bailey, Michael F.; Goldie, Kenneth N.; Karas, John A.; Scanlon, Denis B.; O'Hair, Richard A. J.; Perugini, Matthew A.

    2009-01-01

    Human apolipoprotein C-I (apoC-I) is an exchangeable apolipoprotein that binds to lipoprotein particles in vivo. In this study, we employed a LC-MS/MS assay to demonstrate that residues 38–51 of apoC-I are significantly protected from proteolysis in the presence of 1,2-dimyristoyl-3-sn-glycero-phosphocholine (DMPC). This suggests that the key lipid-binding determinants of apoC-I are located in the C-terminal region, which includes F42 and F46. To test this, we generated site-directed mutants substituting F42 and F46 for glycine or alanine. In contrast to wild-type apoC-I (WT), which binds DMPC vesicles with an apparent Kd [Kd(app)] of 0.89 μM, apoC-I(F42A) and apoC-I(F46A) possess 2-fold weaker affinities for DMPC with Kd(app) of 1.52 μM and 1.58 μM, respectively. However, apoC-I(F46G), apoC-I(F42A/F46A), apoC-I(F42G), and apoC-I(F42G/F46G) bind significantly weaker to DMPC with Kd(app) of 2.24 μM, 3.07 μM, 4.24 μM, and 10.1 μM, respectively. Sedimentation velocity studies subsequently show that the protein/DMPC complexes formed by these apoC-I mutants sediment at 6.5S, 6.7S, 6.5S, and 8.0S, respectively. This is compared with 5.0S for WT apoC-I, suggesting the shape of the particles was different. Transmission electron microscopy confirmed this assertion, demonstrating that WT forms discoidal complexes with a length-to-width ratio of 2.57, compared with 1.92, 2.01, 2.16, and 1.75 for apoC-I(F42G), apoC-I(F46G), apoC-I(F42A/F46A), and apoC-I(F42G/F46G), respectively. Our study demonstrates that the C-terminal amphipathic α-helix of human apoC-I contains the major lipid-binding determinants, including important aromatic residues F42 and F46, which we show play a critical role in stabilizing the structure of apoC-I, mediating phospholipid interactions, and promoting discoidal particle morphology. PMID:18984910

  19. A Virtual State in a Two-Body System Using the Complex Scaling Method

    NASA Astrophysics Data System (ADS)

    Odsuren, M.; Kikuchi, Y.; Myo, T.; Aikawa, M.; Khuukhenkhuu, G.; Katō, K.

    2017-06-01

    In association with the property of the 1/2+ state observed just above the 8Be(0+)+n threshold energy in 9Be, we investigate the photo-disintegration cross section of an s-state in a schematic two-body system using the complex scaling method.

  20. Universal algorithms and programs for calculating the motion parameters in the two-body problem

    NASA Technical Reports Server (NTRS)

    Bakhshiyan, B. T.; Sukhanov, A. A.

    1979-01-01

    The algorithms and FORTRAN programs for computing positions and velocities, orbital elements and first and second partial derivatives in the two-body problem are presented. The algorithms are applicable for any value of eccentricity and are convenient for computing various navigation parameters.

  1. Simple realization of the Fredkin gate using a series of two-body operators

    SciTech Connect

    Chau, H.F.; Wilczek, F.

    1995-07-24

    The Fredkin three-bit gate is universal for computational logic, and is reversible. Classically, it is impossible to do universal computation using reversible two-bit gates only. Here we construct the Fredkin gate using a combination of six two-body reversible (quantum) operators.

  2. Two-body Dirac equation versus KDP equation. [KDP (Kemmer-Duffin-Petiau)

    SciTech Connect

    Aydin, Z.Z.; Yilmazer, A.U. )

    1993-05-01

    A brief review of two-body Dirac and Kemmer-Duffin-Petiau approaches for the bound state problem of two fermions is presented from an algebraic point of view in a comparative manner. Reduction of the direct product of two Dirac spaces is discussed. 12 refs.

  3. 78 FR 54756 - Extension of Expiration Dates for Two Body System Listings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... genitourinary disorders (78 FR 7695) (2013)) and respiratory system disorders (78 FR 7968 (2013)), and revised... ADMINISTRATION 20 CFR Part 404 RIN 0960-AH60 Extension of Expiration Dates for Two Body System Listings AGENCY... following body systems in the Listing of Impairments (listings) in our regulations:...

  4. Orbital Estimation Using Two-Body Classical Orbital Elements as Measurement Updates.

    DTIC Science & Technology

    1979-12-01

    xii I. Introduction .. .. ... ...... ...... ....... 1 II. Truth Model. .. ..... ..... ...... ....... 4 Coordinate Frame...and transmit two-body orbital elements to SDC as measurement updates. This would significantly reduce the data load at SDC. The truth model used in...estimate. The approach taken in this thesis is divided into three parts. First, a truth model will be developed to simulate an actual satellite orbit

  5. Singularity in the Laboratory Frame Angular Distribution Derived in Two-Body Scattering Theory

    ERIC Educational Resources Information Center

    Dick, Frank; Norbury, John W.

    2009-01-01

    The laboratory (lab) frame angular distribution derived in two-body scattering theory exhibits a singularity at the maximum lab scattering angle. The singularity appears in the kinematic factor that transforms the centre of momentum (cm) angular distribution to the lab angular distribution. We show that it is caused in the transformation by the…

  6. Singularity in the Laboratory Frame Angular Distribution Derived in Two-Body Scattering Theory

    ERIC Educational Resources Information Center

    Dick, Frank; Norbury, John W.

    2009-01-01

    The laboratory (lab) frame angular distribution derived in two-body scattering theory exhibits a singularity at the maximum lab scattering angle. The singularity appears in the kinematic factor that transforms the centre of momentum (cm) angular distribution to the lab angular distribution. We show that it is caused in the transformation by the…

  7. Inhibition of TRAF6-Ubc13 interaction in NFkB inflammatory pathway by analyzing the hotspot amino acid residues and protein-protein interactions using molecular docking simulations.

    PubMed

    Biswas, Ria; Bagchi, Angshuman

    2017-10-01

    Protein-protein interactions (PPIs) are important in most of the biochemical processes. Hotspot amino acid residues in proteins are the most important contributors for proper protein-protein interactions. Hotspot amino acid residues have been looked down upon as important therapeutic targets in inhibiting PPIs. Interaction between TRAF6 and Ubc13 is a crucial point in the NFkB inflammatory pathway. Dysfunction of the NFkB pathway is associated with numerous human diseases including cancer and neurodenegeration disorders. Ubc13 also interacts specifically to TRAF6 and not with other proteins of the TRAF family and this makes the TRAF6-Ubc13 complex an important target for specific inhibition. Hence, interfering with the TRAF6-Ubc13 association may prove effective in suppressing the NFkB disease pathway. In the present study, we searched the TRAF6-Ubc13 interaction interface to analyze their binding hotspot amino acid residues using various computational techniques. Heterocyclic compounds are known for their medicinal properties. We screened for heterocyclic analogues to the known TRAF6 inhibitor PDTC, to predict a better inhibitor using in silico protein-ligand and protein-protein interaction studies. Our in silico prediction results suggest that tetrahydro-2-thiophenecarbothioamide (Chemspider ID 36027528) binds one of the major hot-spot residues of TRAF6-Ubc13 interface and can be a better alternative in suppressing TRA6-Ubc13 complex formation in chronic inflammation than PDTC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

    SciTech Connect

    Wildgoose, P.; Kisiel, W.; Kazim, A.L. )

    1990-09-01

    Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 {mu}M. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein.

  9. Arginine 26 and aspartic acid 69 of the regulatory subunit are key residues of subunits interaction of acetohydroxyacid synthase isozyme III from E. coli.

    PubMed

    Zhao, Yuefang; Wen, Xin; Niu, Congwei; Xi, Zhen

    2012-11-05

    Acetohydroxyacid synthase (AHAS), which catalyzes the first step in the biosynthesis of branched-chain amino acids, is composed of catalytic and regulatory subunits. The enzyme exhibits full activity only when the regulatory subunit (RSU) binds to the catalytic subunit (CSU). However, the crystal structure of the holoenzyme has not been reported yet, and the molecular interaction between the CSU and RSU is also unknown. Herein, we introduced a global-surface, site-directed labeling scanning method to determine the potential interaction region of the RSU. This approach relies on the insertion of a bulky fluorescent probe at the designated site on the surface of the RSU to cause a dramatic change in holoenzyme activity by perturbing subunit interaction. Then, the key amino acid residues in the potential interaction regions were identified by site-directed mutagenesis. Compared to the wild-type, the single-point mutants R26A and D69A showed 54 and 64 % activity, respectively, whereas the double mutant (R26A+D69A) gave 14 %, thus suggesting that residues Arg26 and Asp69 are the key residues of subunit interaction with cooperative action. Additionally, the results of GST pull-down assays and pH-dependence experiments suggested that polar interaction is the main force for subunits interaction. A plausible protein-protein interaction model of the holoenzyme of Escherichia coli AHAS III is proposed, based on the mutagenesis and protein docking studies. The protocol established here should be useful for the identification of the molecular interactions between proteins. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Dipicrylamine Modulates GABAρ1 Receptors through Interactions with Residues in the TM4 and Cys-Loop Domains.

    PubMed

    Limon, Agenor; Estrada-Mondragón, Argel; Ruiz, Jorge M Reyes; Miledi, Ricardo

    2016-04-01

    Dipicrylamine (DPA) is a commonly used acceptor agent in Förster resonance energy transfer experiments that allows the study of high-frequency neuronal activity in the optical monitoring of voltage in living cells. However, DPA potently antagonizes GABAA receptors that contain α1 and β2 subunits by a mechanism which is not clearly understood. In this work, we aimed to determine whether DPA modulation is a general phenomenon of Cys-loop ligand-gated ion channels (LGICs), and whether this modulation depends on particular amino acid residues. For this, we studied the effects of DPA on human homomeric GABAρ1, α7 nicotinic, and 5-HT3A serotonin receptors expressed in Xenopus oocytes. Our results indicate that DPA is an allosteric modulator of GABAρ1 receptors with an IC50 of 1.6 µM, an enhancer of α7 nicotinic receptors at relatively high concentrations of DPA, and has little, if any, effect on 5-HT3A receptors. DPA antagonism of GABAρ1 was strongly enhanced by preincubation, was slightly voltage-dependent, and its washout was accelerated by bovine serum albumin. These results indicate that DPA modulation is not a general phenomenon of LGICs, and structural differences between receptors may account for disparities in DPA effects. In silico modeling of DPA docking to GABAρ1, α7 nicotinic, and 5-HT3A receptors suggests that a hydrophobic pocket within the Cys-loop and the M4 segment in GABAρ1, located at the extracellular/membrane interface, facilitates the interaction with DPA that leads to inhibition of the receptor. Functional examinations of mutant receptors support the involvement of the M4 segment in the allosteric modulation of GABAρ1 by DPA.

  11. Association of earthworm-denitrifier interactions with increased emission of nitrous oxide from soil mesocosms amended with crop residue.

    PubMed

    Nebert, Lucas D; Bloem, Jaap; Lubbers, Ingrid M; van Groenigen, Jan Willem

    2011-06-01

    Earthworm activity is known to increase emissions of nitrous oxide (N(2)O) from arable soils. Earthworm gut, casts, and burrows have exhibited higher denitrification activities than the bulk soil, implicating priming of denitrifying organisms as a possible mechanism for this effect. Furthermore, the earthworm feeding strategy may drive N(2)O emissions, as it determines access to fresh organic matter for denitrification. Here, we determined whether interactions between earthworm feeding strategy and the soil denitrifier community can predict N(2)O emissions from the soil. We set up a 90-day mesocosm experiment in which (15)N-labeled maize (Zea mays L.) was either mixed in or applied on top of the soil in the presence or absence of the epigeic earthworm Lumbricus rubellus and/or the endogeic earthworm Aporrectodea caliginosa. We measured N(2)O fluxes and tested the bulk soil for denitrification enzyme activity and the abundance of 16S rRNA and denitrifier genes nirS and nosZ through real-time quantitative PCR. Compared to the control, L. rubellus increased denitrification enzyme activity and N(2)O emissions on days 21 and 90 (day 21, P = 0.034 and P = 0.002, respectively; day 90, P = 0.001 and P = 0.007, respectively), as well as cumulative N(2)O emissions (76%; P = 0.014). A. caliginosa activity led to a transient increase of N(2)O emissions on days 8 to 18 of the experiment. Abundance of nosZ was significantly increased (100%) on day 90 in the treatment mixture containing L. rubellus alone. We conclude that L. rubellus increased cumulative N(2)O emissions by affecting denitrifier community activity via incorporation of fresh residue into the soil and supplying a steady, labile carbon source.

  12. Validation of Proposed Metrics for Two-Body Abrasion Scratch Test Analysis Standards

    NASA Technical Reports Server (NTRS)

    Street, Kenneth W., Jr.; Kobrick, Ryan L.; Klaus, David M.

    2013-01-01

    Abrasion of mechanical components and fabrics by soil on Earth is typically minimized by the effects of atmosphere and water. Potentially abrasive particles lose sharp and pointed geometrical features through erosion. In environments where such erosion does not exist, such as the vacuum of the Moon, particles retain sharp geometries associated with fracturing of their parent particles by micrometeorite impacts. The relationship between hardness of the abrasive and that of the material being abraded is well understood, such that the abrasive ability of a material can be estimated as a function of the ratio of the hardness of the two interacting materials. Knowing the abrasive nature of an environment (abrasive)/construction material is crucial to designing durable equipment for use in such surroundings. The objective of this work was to evaluate a set of standardized metrics proposed for characterizing a surface that has been scratched from a two-body abrasion test. This is achieved by defining a new abrasion region termed Zone of Interaction (ZOI). The ZOI describes the full surface profile of all peaks and valleys, rather than just measuring a scratch width. The ZOI has been found to be at least twice the size of a standard width measurement; in some cases, considerably greater, indicating that at least half of the disturbed surface area would be neglected without this insight. The ZOI is used to calculate a more robust data set of volume measurements that can be used to computationally reconstruct a resultant profile for de tailed analysis. Documenting additional changes to various surface roughness par ameters also allows key material attributes of importance to ultimate design applications to be quantified, such as depth of penetration and final abraded surface roughness. Further - more, by investigating the use of custom scratch tips for specific needs, the usefulness of having an abrasion metric that can measure the displaced volume in this standardized

  13. Machine Learning and Network Analysis of Molecular Dynamics Trajectories Reveal Two Chains of Red/Ox-specific Residue Interactions in Human Protein Disulfide Isomerase.

    PubMed

    Karamzadeh, Razieh; Karimi-Jafari, Mohammad Hossein; Sharifi-Zarchi, Ali; Chitsaz, Hamidreza; Salekdeh, Ghasem Hosseini; Moosavi-Movahedi, Ali Akbar

    2017-06-16

    The human protein disulfide isomerase (hPDI), is an essential four-domain multifunctional enzyme. As a result of disulfide shuffling in its terminal domains, hPDI exists in two oxidation states with different conformational preferences which are important for substrate binding and functional activities. Here, we address the redox-dependent conformational dynamics of hPDI through molecular dynamics (MD) simulations. Collective domain motions are identified by the principal component analysis of MD trajectories and redox-dependent opening-closing structure variations are highlighted on projected free energy landscapes. Then, important structural features that exhibit considerable differences in dynamics of redox states are extracted by statistical machine learning methods. Mapping the structural variations to time series of residue interaction networks also provides a holistic representation of the dynamical redox differences. With emphasizing on persistent long-lasting interactions, an approach is proposed that compiled these time series networks to a single dynamic residue interaction network (DRIN). Differential comparison of DRIN in oxidized and reduced states reveals chains of residue interactions that represent potential allosteric paths between catalytic and ligand binding sites of hPDI.

  14. Transformations of the perturbed two-body problem to unperturbed harmonic oscillators

    NASA Technical Reports Server (NTRS)

    Szebehely, V.; Bond, V.

    1983-01-01

    Singular, nonlinear, and Liapunov unstable equations are made regular and linear through transformations that change the perturbed planar problem of two bodies into unperturbed and undamped harmonic oscillators with constant coefficients, so that the stable solution may be immediately written in terms of the new variables. The use of arbitrary and special functions for the transformations allows the systematic discussion of previously introduced and novel anomalies. For the case of the unperturbed two-body problem, it is proved that if transformations are power functions of the radial variable, only the eccentric and the true anomalies (with the corresponding transformations of the radial variable) will result in harmonic oscillators. The present method significantly reduces computation requirements in autonomous space operations.

  15. Elicitin-Induced Distal Systemic Resistance in Plants is Mediated Through the Protein-Protein Interactions Influenced by Selected Lysine Residues.

    PubMed

    Uhlíková, Hana; Obořil, Michal; Klempová, Jitka; Šedo, Ondrej; Zdráhal, Zbyněk; Kašparovský, Tomáš; Skládal, Petr; Lochman, Jan

    2016-01-01

    Elicitins are a family of small proteins with sterol-binding activity that are secreted by Phytophthora and Pythium sp. classified as oomycete PAMPs. Although α- and β-elicitins bind with the same affinity to one high affinity binding site on the plasma membrane, β-elicitins (possessing 6-7 lysine residues) are generally 50- to 100-fold more active at inducing distal HR and systemic resistance than the α-isoforms (with only 1-3 lysine residues). To examine the role of lysine residues in elicitin biological activity, we employed site-directed mutagenesis to prepare a series of β-elicitin cryptogein variants with mutations on specific lysine residues. In contrast to direct infiltration of protein into leaves, application to the stem revealed a rough correlation between protein's charge and biological activity, resulting in protection against Phytophthora parasitica. A detailed analysis of proteins' movement in plants showed no substantial differences in distribution through phloem indicating differences in consequent apoplastic or symplastic transport. In this process, an important role of homodimer formation together with the ability to form a heterodimer with potential partner represented by endogenous plants LTPs is suggested. Our work demonstrates a key role of selected lysine residues in these interactions and stresses the importance of processes preceding elicitin recognition responsible for induction of distal systemic resistance.

  16. Elicitin-Induced Distal Systemic Resistance in Plants is Mediated Through the Protein–Protein Interactions Influenced by Selected Lysine Residues

    PubMed Central

    Uhlíková, Hana; Obořil, Michal; Klempová, Jitka; Šedo, Ondrej; Zdráhal, Zbyněk; Kašparovský, Tomáš; Skládal, Petr; Lochman, Jan

    2016-01-01

    Elicitins are a family of small proteins with sterol-binding activity that are secreted by Phytophthora and Pythium sp. classified as oomycete PAMPs. Although α- and β-elicitins bind with the same affinity to one high affinity binding site on the plasma membrane, β-elicitins (possessing 6–7 lysine residues) are generally 50- to 100-fold more active at inducing distal HR and systemic resistance than the α-isoforms (with only 1–3 lysine residues). To examine the role of lysine residues in elicitin biological activity, we employed site-directed mutagenesis to prepare a series of β-elicitin cryptogein variants with mutations on specific lysine residues. In contrast to direct infiltration of protein into leaves, application to the stem revealed a rough correlation between protein’s charge and biological activity, resulting in protection against Phytophthora parasitica. A detailed analysis of proteins’ movement in plants showed no substantial differences in distribution through phloem indicating differences in consequent apoplastic or symplastic transport. In this process, an important role of homodimer formation together with the ability to form a heterodimer with potential partner represented by endogenous plants LTPs is suggested. Our work demonstrates a key role of selected lysine residues in these interactions and stresses the importance of processes preceding elicitin recognition responsible for induction of distal systemic resistance. PMID:26904041

  17. Role of enthalpy-entropy compensation interactions in determining the conformational propensities of amino acid residues in unfolded peptides.

    PubMed

    Toal, Siobhan E; Verbaro, Daniel J; Schweitzer-Stenner, Reinhard

    2014-02-06

    The driving forces governing the unique and restricted conformational preferences of amino acid residues in the unfolded state are still not well understood. In this study, we experimentally determine the individual thermodynamic components underlying intrinsic conformational propensities of these residues. Thermodynamic analysis of ultraviolet-circular dichroism (UV-CD) and (1)H NMR data for a series of glycine capped amino acid residues (i.e., G-x-G peptides) reveals the existence of a nearly exact enthalpy-entropy compensation for the polyproline II-β strand equilibrium for all investigated residues. The respective ΔHβ, ΔSβ values exhibit a nearly perfect linear relationship with an apparent compensation temperature of 295 ± 2 K. Moreover, we identified iso-equilibrium points for two subsets of residues at 297 and 305 K. Thus, our data suggest that within this temperature regime, which is only slightly below physiological temperatures, the conformational ensembles of amino acid residues in the unfolded state differ solely with respect to their capability to adopt turn-like conformations. Such iso-equilibria are rarely observed, and their existence herein indicates a common physical origin behind conformational preferences, which we are able to assign to side-chain dependent backbone solvation. Conformational effects such as differences between the number of sterically allowed side chain rotamers can contribute to enthalpy and entropy but not to the Gibbs energy associated with conformational preferences. Interestingly, we found that alanine, aspartic acid, and threonine are the only residues which do not share these iso-equilbiria. The enthalpy-entropy compensation discovered as well as the iso-equilbrium and thermodynamics obtained for each amino acid residue provide a new and informative way of identifying the determinants of amino acid propensities in unfolded and disordered states.

  18. Coiled-coil interaction of N-terminal 36 residues of cyclase-associated protein with adenylyl cyclase is sufficient for its function in Saccharomyces cerevisiae ras pathway.

    PubMed

    Nishida, Y; Shima, F; Sen, H; Tanaka, Y; Yanagihara, C; Yamawaki-Kataoka, Y; Kariya, K; Kataoka, T

    1998-10-23

    In the budding yeast Saccharomyces cerevisiae, association with the 70-kDa cyclase-associated protein (CAP) is required for proper response of adenylyl cyclase to Ras proteins. We show here that a small segment comprising the N-terminal 36 amino acid residues of CAP is sufficient for association with adenylyl cyclase as well as for its function in the Ras-adenylyl cyclase pathway as assayed by the ability to confer RAS2(Val-19)-dependent heat shock sensitivity to yeast cells. The CAP-binding site of adenylyl cyclase was mapped to a segment of 119 amino acid residues near its C terminus. Both of these regions contained tandem repetitions of a heptad motif alphaXXalphaXXX (where alpha represents a hydrophobic amino acid and X represents any amino acid), suggesting a coiled-coil interaction. When mutants of CAP defective in associating with adenylyl cyclase were isolated by screening of a pool of randomly mutagenized CAP, they were found to carry substitution mutations in one of the key hydrophobic residues in the heptad repeats. Furthermore, mutations of the key hydrophobic residues in the heptad repeats of adenylyl cyclase also resulted in loss of association with CAP. These results indicate the coiled-coil mechanism as a basis of the CAP-adenylyl cyclase interaction.

  19. The Presence of Modifiable Residues in the Core Peptide Part of Precursor Nisin Is Not Crucial for Precursor Nisin Interactions with NisB- and NisC

    PubMed Central

    Khusainov, Rustem; Kuipers, Oscar P.

    2013-01-01

    Precursor nisin is a model posttranslationally modified precursor lantibiotic that can be structurally divided into a leader peptide sequence and a modifiable core peptide part. The nisin core peptide clearly plays an important role in the precursor nisin – nisin modification enzymes interactions, since it has previously been shown that the construct containing only the nisin leader sequence is not sufficient to pull-down the nisin modification enzymes NisB and NisC. Serines and threonines in the core peptide part are the residues that NisB specifically dehydrates, and cysteines are the residues that NisC stereospecifically couples to the dehydrated amino acids. Here, we demonstrate that increasing the number of negatively charged residues in the core peptide part of precursor nisin, which are absent in wild-type nisin, does not abolish binding of precursor nisin to the modification enzymes NisB and NisC, but dramatically decreases the antimicrobial potency of these nisin mutants. An unnatural precursor nisin variant lacking all serines and threonines in the core peptide part and an unnatural precursor nisin variant lacking all cysteines in the core peptide part still bind the nisin modification enzymes NisB and NisC, suggesting that these residues are not essential for direct interactions with the nisin modification enzymes NisB and NisC. These results are important for lantibiotic engineering studies. PMID:24040355

  20. [An extension strategy of Discovery Studio 2.0 for non-bonded interaction energy automatic calculation at the residue level].

    PubMed

    Gao, Yue-Dong; Huang, Jing-Fei

    2011-06-01

    Non-bonded interaction forces play crucial roles in molecular recognition and binding in biological systems. However, it is difficult for traditional methods to automatically calculate and batch the non-bonded energy at the residue level. In recent years, many studies have focused on non-bonded interactions and developed tools to calculate and analyze such interactions. In this study, we present a highly automated approach for the calculation of non-bonded energy. Our strategy invoked protocols relevant to non-bonded interactions within Discovery Studio 2.0 (DS2.0, Accelrys Inc.) bottom module using Perl script, and determined the direct command line operation of calculating non-bonded interaction energy batches without accessing the graphical interface of DS. This approach extended the DS2.0 module and was applied to a recent study of complex structure analysis.

  1. Two-body relaxation driven evolution of the young stellar disk in the galactic center

    SciTech Connect

    Šubr, Ladislav; Haas, Jaroslav

    2014-05-10

    The center of our Galaxy hosts almost two hundred very young stars, a subset of which is orbiting the central supermassive black hole (SMBH) in a relatively thin disk-like structure. First analyses indicated a power-law surface density profile of the disk, Σ∝R {sup β} with β = –2. Recently, however, doubts about this profile arose. In particular, it now seems to be better described by a sort of broken power law. By means of both analytical arguments and numerical N-body modeling, we show that such a broken power-law profile is a natural consequence of the two-body relaxation of the disk. Due to the small relative velocities of the nearby stars in co-planar Keplerian orbits around the SMBH, two-body relaxation is effective enough to affect the evolution of the disk on timescales comparable to its estimated age. In the inner, densest part of the disk, the profile becomes rather flat (β ≈ –1) while the outer parts keep imprints of the initial state. Our numerical models show that the observed projected surface density profile of the young stellar disk can result from two-body relaxation driven evolution of a disk with initial single power-law profile with –2 ≲ β ≲ –1.5. In addition, we suggest that two-body relaxation may have caused a significant radial migration of the S-stars toward the central SMBH, thus playing an important role in their formation scenario.

  2. Multipolar polarizabilities and two-body dispersion coefficients for Na by a variationally stable procedure

    NASA Astrophysics Data System (ADS)

    Sun, Qiu-Feng; Huang, Shi-Zhong

    2011-11-01

    Based on the weakest bound electron potential model theory, the ground-state wave function of Na is investigated. The variationally stable procedure of Gao and Starace is then employed to evaluate the static multipolar polarizabilities of Na, and the two-body dispersion coefficients for the Na-Na system. Calculated values show that our results are in general agreement with those previously reported in the literature.

  3. Specific Residues of a Conserved Domain in the N Terminus of the Human Cytomegalovirus pUL50 Protein Determine Its Intranuclear Interaction with pUL53*

    PubMed Central

    Milbradt, Jens; Auerochs, Sabrina; Sevvana, Madhumati; Muller, Yves A.; Sticht, Heinrich; Marschall, Manfred

    2012-01-01

    Herpesviral capsids are assembled in the host cell nucleus and are subsequently translocated to the cytoplasm. During this process it has been demonstrated that the human cytomegalovirus proteins pUL50 and pUL53 interact and form, together with other viral and cellular proteins, the nuclear egress complex at the nuclear envelope. In this study we provide evidence that specific residues of a conserved N-terminal region of pUL50 determine its intranuclear interaction with pUL53. In silico evaluation and biophysical analyses suggested that the conserved region forms a regular secondary structure adopting a globular fold. Importantly, site-directed replacement of individual amino acids by alanine indicated a strong functional influence of specific residues inside this globular domain. In particular, mutation of the widely conserved residues Glu-56 or Tyr-57 led to a loss of interaction with pUL53. Consistent with the loss of binding properties, mutants E56A and Y57A showed a defective function in the recruitment of pUL53 to the nuclear envelope in expression plasmid-transfected and human cytomegalovirus-infected cells. In addition, in silico analysis suggested that residues 3–20 form an amphipathic α-helix that appears to be conserved among Herpesviridae. Point mutants revealed a structural role of this N-terminal α-helix for pUL50 stability rather than a direct role in the binding of pUL53. In contrast, the central part of the globular domain including Glu-56 and Tyr-57 is directly responsible for the functional interaction with pUL53 and thus determines formation of the basic nuclear egress complex. PMID:22589554

  4. Water-soluble LYNX1 residues important for interaction with muscle-type and/or neuronal nicotinic receptors.

    PubMed

    Lyukmanova, Ekaterina N; Shulepko, Mikhail A; Buldakova, Svetlana L; Kasheverov, Igor E; Shenkarev, Zakhar O; Reshetnikov, Roman V; Filkin, Sergey Y; Kudryavtsev, Denis S; Ojomoko, Lucy O; Kryukova, Elena V; Dolgikh, Dmitry A; Kirpichnikov, Mikhail P; Bregestovski, Piotr D; Tsetlin, Victor I

    2013-05-31

    Human LYNX1, belonging to the Ly6/neurotoxin family of three-finger proteins, is membrane-tethered with a glycosylphosphatidylinositol anchor and modulates the activity of nicotinic acetylcholine receptors (nAChR). Recent preparation of LYNX1 as an individual protein in the form of water-soluble domain lacking glycosylphosphatidylinositol anchor (ws-LYNX1; Lyukmanova, E. N., Shenkarev, Z. O., Shulepko, M. A., Mineev, K. S., D'Hoedt, D., Kasheverov, I. E., Filkin, S. Y., Krivolapova, A. P., Janickova, H., Dolezal, V., Dolgikh, D. A., Arseniev, A. S., Bertrand, D., Tsetlin, V. I., and Kirpichnikov, M. P. (2011) NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J. Biol. Chem. 286, 10618-10627) revealed the attachment at the agonist-binding site in the acetylcholine-binding protein (AChBP) and muscle nAChR but outside it, in the neuronal nAChRs. Here, we obtained a series of ws-LYNX1 mutants (T35A, P36A, T37A, R38A, K40A, Y54A, Y57A, K59A) and examined by radioligand analysis or patch clamp technique their interaction with the AChBP, Torpedo californica nAChR and chimeric receptor composed of the α7 nAChR extracellular ligand-binding domain and the transmembrane domain of α1 glycine receptor (α7-GlyR). Against AChBP, there was either no change in activity (T35A, T37A), slight decrease (K40A, K59A), and even enhancement for the rest mutants (most pronounced for P36A and R38A). With both receptors, many mutants lost inhibitory activity, but the increased inhibition was observed for P36A at α7-GlyR. Thus, there are subtype-specific and common ws-LYNX1 residues recognizing distinct targets. Because ws-LYNX1 was inactive against glycine receptor, its "non-classical" binding sites on α7 nAChR should be within the extracellular domain. Micromolar affinities and fast washout rates measured for ws-LYNX1 and its mutants are in contrast to nanomolar affinities and irreversibility of binding for α-bungarotoxin and similar

  5. Water-soluble LYNX1 Residues Important for Interaction with Muscle-type and/or Neuronal Nicotinic Receptors*

    PubMed Central

    Lyukmanova, Ekaterina N.; Shulepko, Mikhail A.; Buldakova, Svetlana L.; Kasheverov, Igor E.; Shenkarev, Zakhar O.; Reshetnikov, Roman V.; Filkin, Sergey Y.; Kudryavtsev, Denis S.; Ojomoko, Lucy O.; Kryukova, Elena V.; Dolgikh, Dmitry A.; Kirpichnikov, Mikhail P.; Bregestovski, Piotr D.; Tsetlin, Victor I.

    2013-01-01

    Human LYNX1, belonging to the Ly6/neurotoxin family of three-finger proteins, is membrane-tethered with a glycosylphosphatidylinositol anchor and modulates the activity of nicotinic acetylcholine receptors (nAChR). Recent preparation of LYNX1 as an individual protein in the form of water-soluble domain lacking glycosylphosphatidylinositol anchor (ws-LYNX1; Lyukmanova, E. N., Shenkarev, Z. O., Shulepko, M. A., Mineev, K. S., D'Hoedt, D., Kasheverov, I. E., Filkin, S. Y., Krivolapova, A. P., Janickova, H., Dolezal, V., Dolgikh, D. A., Arseniev, A. S., Bertrand, D., Tsetlin, V. I., and Kirpichnikov, M. P. (2011) NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J. Biol. Chem. 286, 10618–10627) revealed the attachment at the agonist-binding site in the acetylcholine-binding protein (AChBP) and muscle nAChR but outside it, in the neuronal nAChRs. Here, we obtained a series of ws-LYNX1 mutants (T35A, P36A, T37A, R38A, K40A, Y54A, Y57A, K59A) and examined by radioligand analysis or patch clamp technique their interaction with the AChBP, Torpedo californica nAChR and chimeric receptor composed of the α7 nAChR extracellular ligand-binding domain and the transmembrane domain of α1 glycine receptor (α7-GlyR). Against AChBP, there was either no change in activity (T35A, T37A), slight decrease (K40A, K59A), and even enhancement for the rest mutants (most pronounced for P36A and R38A). With both receptors, many mutants lost inhibitory activity, but the increased inhibition was observed for P36A at α7-GlyR. Thus, there are subtype-specific and common ws-LYNX1 residues recognizing distinct targets. Because ws-LYNX1 was inactive against glycine receptor, its “non-classical” binding sites on α7 nAChR should be within the extracellular domain. Micromolar affinities and fast washout rates measured for ws-LYNX1 and its mutants are in contrast to nanomolar affinities and irreversibility of binding for α-bungarotoxin and

  6. Actions between neonicotinoids and key residues of insect nAChR based on an ab initio quantum chemistry study: hydrogen bonding and cooperative pi-pi interaction.

    PubMed

    Wang, Yanli; Cheng, Jiagao; Qian, Xuhong; Li, Zhong

    2007-04-01

    Neonicotinoid insecticides show selective actions on insect nicotinic acetylcholine receptor (nAChR). Two key residues (Trp and Arg/Lys) have been identified as contributing to the neonicotinois binding. To investigate the selective mechanism, a computational model was set up to simulate the interaction between residues (Trp and Arg) of insect nAChR and neonicotinoids by quantum chemistry method. Three analogues of neonicotinoid derivatives without the chloropyridinyl moiety and 3-methyl-indole (3MI), guanidinium (Gua) were used to mimic the neonicotinoids and the side chain of key residues Trp and Arg accordingly. Interaction features of 3MI-analogues, analogues-Gua and 3MI-analogues -Gua complexes were analyzed comparatively. Hydrogen bonding between the nitro group of analogues and Gua was found to be the most important for binding. Moreover, the cooperative pi-pi interaction between analogues and the indole ring, which is strengthened by the existence of Gua, also contributes to the binding. The alternative binding model of neonicotinoids proposed here, although slightly different from others, might be close to the actual.

  7. A transmembrane residue influences the interaction of propofol with the strychnine-sensitive glycine alpha1 and alpha1beta receptor.

    PubMed

    Ahrens, Jörg; Leuwer, Martin; Stachura, Sina; Krampfl, Klaus; Belelli, Delia; Lambert, Jeremy J; Haeseler, Gertrud

    2008-12-01

    Propofol, well known for its anesthetic effects, acts as a positive allosteric modulator of the alpha-aminobutyric acid type A (GABA(A)) receptor but also enhances the function of the glycine receptor. The GABA modulatory effects of propofol are influenced by an amino acid residue located within the second transmembrane domain (TM2) of the GABA(A) receptor beta subunit. In glycine alpha(1) subunits, the homologous residue (serine 267) affects the glycine modulatory actions of alcohols and alkane anesthetics. In the present study we investigated the role of this residue on the interaction of propofol with the glycine alpha(1) and alpha(1)beta receptor. The influence of propofol on wild type and mutant (alpha(1)S267M, alpha(1)S267I, alpha(1)S267Mbeta, alpha(1)S267Ibeta) glycine receptors expressed in human embryonic kidney 293 cells was investigated by using the whole-cell clamp technique. Mutation of the alpha(1) subunit TM2 serine residue to either isoleucine or methionine decreased the sensitivity of the receptor to glycine, and abolished the direct activation of the glycine receptor by propofol. Additionally, the methionine and particularly the isoleucine mutation decreased the glycine-enhancing actions of propofol. The nature of the TM2 residue (267) of the glycine alpha(1) subunit influences the glycine modulatory effect of propofol and direct activation of the receptor by this anesthetic. A comparison of the impact of such complementary mutations on the interaction of propofol with glycine and GABA(A) receptors should permit a better understanding of the molecular determinants of action of propofol on these structurally related receptors and may aid in the development of selective glycine receptor modulators.

  8. Effect of D to E mutation of the RGD motif in rhodostomin on its activity, structure, and dynamics: importance of the interactions between the D residue and integrin.

    PubMed

    Chen, Chiu-Yueh; Shiu, Jia-Hau; Hsieh, Yao-Husn; Liu, Yu-Chen; Chen, Yen-Chin; Chen, Yi-Chun; Jeng, Wen-Yih; Tang, Ming-Jer; Lo, Szecheng J; Chuang, Woei-Jer

    2009-09-01

    Rhodostomin (Rho) is a snake venom protein containing an RGD motif that specifically inhibits the integrin-binding function. Rho produced in Pichia pastoris inhibits platelet aggregation with a K(I) of 78 nM as potent as native Rho. In contrast, its D51E mutant inhibits platelet aggregation with a K(I) of 49 muM. Structural analysis of Rho and its D51E mutant showed that they have the same tertiary fold with three two-stranded antiparallel beta-sheets. There are no structural backbone differences between the RG[D/E] loop which extends outward from the protein core and the RG[D/E] sequence at its apex in a four-residue RG[D/E]M type I turn. Two minor differences between Rho and its D51E mutant were only found from their backbone dynamics and 3D structures. The R(2) value of E51 is 13% higher than that of the D51 residue. A difference in the charge separation of 1.76 A was found between the sidechains of positive (R49) and negative residues (D51 or E51).The docking of Rho into integrin alphavbeta3 showed that the backbone amide and carbonyl groups of the D51 residue of Rho were formed hydrogen bonds with the integrin residues R216 and R214, respectively. In contrast, these hydrogen bonds were absent in the D51E mutant-integrin complex. Our findings suggest that the interactions between both the sidechain and backbone of the D residue of RGD-containing ligands and integrin are important for their binding. Copyright 2009 Wiley-Liss, Inc.

  9. Lone pair ... pi interactions between water oxygens and aromatic residues: quantum chemical studies based on high-resolution protein structures and model compounds.

    PubMed

    Jain, Alok; Ramanathan, Venkatnarayan; Sankararamakrishnan, Ramasubbu

    2009-03-01

    The pi electron cloud of aromatic centers is known to be involved in several noncovalent interactions such as C--H...pi, O--H...pi, and pi...pi interactions in biomolecules. Lone-pair (lp) ... pi interactions have gained attention recently and their role in biomolecular structures is being recognized. In this article, we have carried out systematic analysis of high-resolution protein structures and identified more than 400 examples in which water oxygen atoms are in close contact (distance < 3.5 A) with the aromatic centers of aromatic residues. Three different methods were used to build hydrogen atoms and we used a consensus approach to find out potential candidates for lp...pi interactions between water oxygen and aromatic residues. Quantum mechanical calculations at MP2/6-311++G(d,p) level on model systems based on protein structures indicate that majority of the identified examples have energetically favorable interactions. The influence of water hydrogen atoms was investigated by sampling water orientations as a function of two parameters: distance from the aromatic center and the angle between the aromatic plane and the plane formed by the three water atoms. Intermolecular potential surfaces were constructed using six model compounds representing the four aromatic amino acids and 510 different water orientations for each model compound. Ab initio molecular orbital calculations at MP2/6-311++G(d,p) level show that the interaction energy is favorable even when hydrogen atoms are farthest from the aromatic plane while water oxygen is pointing toward the aromatic center. The strength of such interaction depends upon the distance of water hydrogen atoms from the aromatic substituents. Our calculations clearly show that the lp...pi interactions due to the close approach of water oxygen and aromatic center are influenced by the positions of water hydrogen atoms and the aromatic substituents.

  10. Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution: exploring the applications of high-resolution genetic interaction mapping of point mutations.

    PubMed

    Braberg, Hannes; Moehle, Erica A; Shales, Michael; Guthrie, Christine; Krogan, Nevan J

    2014-07-01

    We have achieved a residue-level resolution of genetic interaction mapping - a technique that measures how the function of one gene is affected by the alteration of a second gene - by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine.

  11. Virtual-state character of the two-body system in the complex scaling method

    NASA Astrophysics Data System (ADS)

    Odsuren, Myagmarjav; Kikuchi, Yuma; Myo, Takayuki; Khuukhenkhuu, Gonchigdorj; Masui, Hiroshi; Katō, Kiyoshi

    2017-06-01

    In association with the property of the 1 /2+ state observed just above the 8Be(0+)+n threshold energy in 9Be, we investigate the photodisintegration cross section of an s state in a simple schematic two-body model using the complex scaling method. The photodisintegration cross section, continuum level density, scattering phase shifts, and scattering length are discussed in relation with the virtual state. These scattering observables show strong divergences when a virtual state is located near the physical scattering region.

  12. Phase-space structure of the Buckingham's two-body problem

    NASA Astrophysics Data System (ADS)

    Pricopi, D.; Popescu, E.

    2016-06-01

    In this paper, we study the global flow for the two-body problem associated to the Buckingham potential. For this, using McGehee-type transformations, we write the regularized equations of motion. Then, reducing the 4-dimensional phase space to a 2-dimension one, the global flow in the phase plane is described for all possible values of the parameters of the potential and those of the energy and angular momentum constants. Every phase trajectory is interpreted in terms of physical motion, our problem being depicted both geometrically and physically.

  13. Data-adaptive unfolding of nonergodic spectra: Two-Body Random Ensemble

    NASA Astrophysics Data System (ADS)

    Fossion, R.; Torres Vargas, G.; Velázquez, V.; López Vieyra, J. C.

    2015-01-01

    The statistics of spectral fluctuations is sensitive to the unfolding procedure that separates global from local properties. Previously, we presented a parameter-free and data- adaptive unfolding method that we demonstrated to be highly effective for standard random- matrix ensembles from Random Matrix Theory (RMT). More general ensembles often break the ergodicity property, which leads to ambiguities between individual-spectrum averaged and ensemble-averaged fluctuation measures. Here, we apply our data-adaptive unfolding to a nonergodic Two-Body Random Ensemble (TBRE). In the present approach, both fluctuation measures can be calculated simultaneously within the same unfolding step, and possible arbitrarities introduced by traditional unfolding procedures are avoided.

  14. Construction of Effective Electromagnetic Currents for Two-Body Quasipotential Equations

    SciTech Connect

    Krioukov, Dmitri

    1998-09-01

    A systematic algebraic approach for the construction of effective electro-magnetic currents consistent with relativistic two-body quasipotential equations is presented. This approach generalizes the Mandelstam formalism and applies it to a generic quasipotential reduction method. The use of Ward-Takahashi identities for the effective currents guarantees conservation of current matrix elements involving any combination of bound and scattering states. This approach is shown to reproduce previous results for current matrix elements for the particular cases of the Gross and Blankenbecler-Sugar equations. A generic method of truncation of the quasipotential effective current with respect to the number of boson exchanges is introduced.

  15. Probing SUSY CP violation in two-body stop decays at the LHC

    NASA Astrophysics Data System (ADS)

    Deppisch, Frank F.; Kittel, Olaf

    2009-09-01

    We study CP asymmetries in two-body decays of top squarks into neutralinos and sleptons at the LHC. These asymmetries are used to probe the CP phases possibly present in the stop and neutralino sector of the Minimal Supersymmetric Standard Model. Taking into account bounds from experimental electric dipole moment searches, we identify areas in the mSUGRA parameter space where CP asymmetries can be sizeable and discuss the feasibility of their observation at the LHC. As a result, potentially detectable CP asymmetries in stop decays at the LHC are found, motivating further detailed experimental studies for probing SUSY CP phases.

  16. The number of cysteine residues per mole in apolipoprotein E affects systematically synchronous neural interactions in women's healthy brains.

    PubMed

    Leuthold, Arthur C; Mahan, Margaret Y; Stanwyck, John J; Georgopoulos, Angeliki; Georgopoulos, Apostolos P

    2013-05-01

    Apolipoprotein E (apoE) is involved in lipid metabolism in the brain, but its effects on brain function are not understood. Three apoE isoforms (E4, E3, and E2) are the result of cysteine-arginine interchanges at two sites: there are zero interchanges in E4, one interchange in E3, and two interchanges in E2. The resulting six apoE genotypes (E4/4, E4/3, E4/2, E3/3, E3/2, E2/2) yield five groups with respect to the number of cysteine residues per mole (CysR/mole), as follows. ApoE4/4 has zero cysteine residues per mole (0-CysR/mole), E4/3 has one (1-CysR/mole), E4/2 and E3/3 each has two (2-CysR/mole), E3/2 has three (3-CysR/mole), and E2/2 has four (4-CysR/mole). The use of the number of CysR/mole to characterize the apoE molecule converts the categorical apoE genotype scale, consisting of 6 distinct genotypes above, to a 5-point continuous scale (0-4 CysR/mole). This allows the use of statistical analyses suitable for continuous variables (e.g. regression) to quantify the relations between various variables and apoE. Using such analyses, here, we show for the first time that apoE affects in a graded and orderly manner neural communication, as assessed by analyzing the relation between the number of CysR/mole and synchronous neural interactions (SNI) measured by magnetoencephalography (MEG) in 130 cognitively healthy women. At the one end of the CysR/mole range, the 4-CysR/mole (E2/2) SNI distribution had the highest mean, lowest variance, lowest range, and lowest coefficient of variation, whereas at the other end, 0-CysR/mole (E4/4) SNI distribution had the lowest mean, highest variance, highest range, and highest coefficient of variation. The special status of the 4-CysR/mole distribution was reinforced by the results of a hierarchical tree analysis where the 4-CysR/mole (E2/2) SNI distribution occupied a separate branch by itself and the remaining CysR/mole SNI distributions were placed at increasing distances from the 4-CysR/mole distribution, according to

  17. Addition of a clay subsoil to a sandy top soil alters CO2 release and the interactions in residue mixtures.

    PubMed

    Shi, Andong; Marschner, Petra

    2013-11-01

    Addition of clay-rich subsoils to sandy top soils is an agricultural management option to increase water and nutrient retention and may also increase organic carbon sequestration by decreasing the decomposition rates. An incubation experiment was carried out in a loamy sand top soil mixed with a clay-rich subsoil (84% clay) at 0, 10 and 30% (w/w) amended with finely ground mature shoot residues of two native perennial grasses and annual barley individually or in 1:1 mixtures of two residues. Extractable C, microbial biomass C, available N and soil pH were analysed at days 0, 3, 14 and 28. Cumulative respiration after 28 days was highest with barley residue and lowest with Wallaby grass at all clay soil addition rates; 30% clay soil addition reduced cumulative respiration, especially with barley alone. In the mixture of native grasses and barley, the measured respiration was lower than expected at a clay soil addition rate of 10%. A synergistic effect (higher than expected cumulative respiration) was only found in mixture of Kangaroo grass and barley at a clay soil addition rate of 30%. Clay soil addition also decreased extractable C, available N and soil pH. The temporal change in microbial biomass C and available N in residue mixtures differed among clay addition rates. In the mixture of Wallaby grass and Kangaroo grass, microbial biomass C (MBC) decreased from day 0 to day 28 at clay soil addition rates of 0 and 10%, whereas at 30% clay MBC increased from day 0 to day 3 and then decreased. Our study shows that addition of a clay-rich subsoil to a loamy sand soil can increase C sequestration by reducing CO2 release and extractable C which are further modulated by the type of residues present individually or as mixtures. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Role of Acidic Residues in Helices TH8–TH9 in Membrane Interactions of the Diphtheria Toxin T Domain

    PubMed Central

    Ghatak, Chiranjib; Rodnin, Mykola V.; Vargas-Uribe, Mauricio; McCluskey, Andrew J.; Flores-Canales, Jose C.; Kurnikova, Maria; Ladokhin, Alexey S.

    2015-01-01

    The pH-triggered membrane insertion of the diphtheria toxin translocation domain (T domain) results in transferring the catalytic domain into the cytosol, which is relevant to potential biomedical applications as a cargo-delivery system. Protonation of residues is suggested to play a key role in the process, and residues E349, D352 and E362 are of particular interest because of their location within the membrane insertion unit TH8–TH9. We have used various spectroscopic, computational and functional assays to characterize the properties of the T domain carrying the double mutation E349Q/D352N or the single mutation E362Q. Vesicle leakage measurements indicate that both mutants interact with the membrane under less acidic conditions than the wild-type. Thermal unfolding and fluorescence measurements, complemented with molecular dynamics simulations, suggest that the mutant E362Q is more susceptible to acid destabilization because of disruption of native intramolecular contacts. Fluorescence experiments show that removal of the charge in E362Q, and not in E349Q/D352N, is important for insertion of TH8–TH9. Both mutants adopt a final functional state upon further acidification. We conclude that these acidic residues are involved in the pH-dependent action of the T domain, and their replacements can be used for fine tuning the pH range of membrane interactions. PMID:25875295

  19. A Residue Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions.

    PubMed

    Saltzberg, Daniel John; Broughton, Howard B; Pellarin, Riccardo; Chalmers, Michael J; Espada, Alfonso; Dodge, Jeffrey A; Pascal, Bruce D; Griffin, Patrick R; Humblet, Christine; Sali, Andrej

    2016-11-03

    Characterization of interactions between proteins and other molecules is crucial for understanding the mechanisms of action of biological systems and, thus, drug discovery. An increasingly useful approach to mapping these interactions is measurement of hydrogen/deuterium exchange (HDX) using mass spectrometry (HDX-MS), which measures the time-resolved deuterium incorporation of peptides obtained by enzymatic digestion of the protein. Comparison of exchange rates between apo- and ligand-bound conditions results in a mapping of the differential HDX (ΔHDX) of the ligand. Residue-level analysis of these data, however, must account for experimental error, sparseness and ambiguity due to overlapping peptides. Here, we propose a Bayesian method consisting of a forward model, noise model, prior probabilities, and a Monte Carlo sampling scheme. This method exploits a residue-resolved exponential rate model of HDX-MS data obtained from all peptides simultaneously, and explicitly models experimental error. The result is the best possible estimate of ΔHDX magnitude and significance for each residue given the data. We demonstrate the method by revealing richer structural interpretation of ΔHDX data on two nuclear receptors: vitamin D-receptor (VDR) and retinoic acid receptor gamma (RORγ). The method is implemented in HDX Workbench and as a standalone module of the open source Integrative Modeling Platform.

  20. Interaction between DNA Gyrase and Quinolones: Effects of Alanine Mutations at GyrA Subunit Residues Ser83 and Asp87

    PubMed Central

    Barnard, Faye M.; Maxwell, Anthony

    2001-01-01

    DNA gyrase is a target of quinolone antibacterial agents, but the molecular details of the quinolone-gyrase interaction are not clear. Quinolone resistance mutations frequently occur at residues Ser83 and Asp87 of the gyrase A subunit, suggesting that these residues are involved in drug binding. Single and double alanine substitutions were created at these positions (Ala83, Ala87, and Ala83 Ala87), and the mutant proteins were assessed for DNA supercoiling, DNA cleavage, and resistance to a number of quinolone drugs. The Ala83 mutant was fully active in supercoiling, whereas the Ala87 and the double mutant were 2.5- and 4- to 5-fold less active, respectively; this loss in activity may be partly due to an increased affinity of these mutant proteins for DNA. Supercoiling inhibition and cleavage assays revealed that the double mutant has a high level of resistance to certain quinolones while the mutants with single alanine substitutions show low-level resistance. Using a drug-binding assay we demonstrated that the double-mutant enzyme-DNA complex has a lower affinity for ciprofloxacin than the wild-type complex. Based on the pattern of resistance to a series of quinolones, an interaction between the C-8 group of the quinolone and the double-mutant gyrase in the region of residues 83 and 87 is proposed. PMID:11408214

  1. An integrated molecular dynamics, principal component analysis and residue interaction network approach reveals the impact of M184V mutation on HIV reverse transcriptase resistance to lamivudine.

    PubMed

    Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

    2014-08-01

    The emergence of different drug resistant strains of HIV-1 reverse transcriptase (HIV RT) remains of prime interest in relation to viral pathogenesis as well as drug development. Amongst those mutations, M184V was found to cause a complete loss of ligand fitness. In this study, we report the first account of the molecular impact of M184V mutation on HIV RT resistance to 3TC (lamivudine) using an integrated computational approach. This involved molecular dynamics simulation, binding free energy analysis, principle component analysis (PCA) and residue interaction networks (RINs). Results clearly confirmed that M184V mutation leads to steric conflict between 3TC and the beta branched side chain of valine, decreases the ligand (3TC) binding affinity by ∼7 kcal mol(-1) when compared to the wild type, changes the overall conformational landscape of the protein and distorts the native enzyme residue-residue interaction network. The comprehensive molecular insight gained from this study should be of great importance in understanding drug resistance against HIV RT as well as assisting in the design of novel reverse transcriptase inhibitors with high ligand efficacy on resistant strains.

  2. Herpes Simplex Virus 1 UL37 Protein Tyrosine Residues Conserved among All Alphaherpesviruses Are Required for Interactions with Glycoprotein K, Cytoplasmic Virion Envelopment, and Infectious Virus Production

    PubMed Central

    Chouljenko, Dmitry V.; Jambunathan, Nithya; Chouljenko, Vladimir N.; Naderi, Misagh; Brylinski, Michal; Caskey, John R.

    2016-01-01

    ABSTRACT The herpes simplex virus 1 (HSV-1) UL37 protein functions in virion envelopment at trans-Golgi membranes, as well as in retrograde and anterograde transport of virion capsids. Recently, we reported that UL37 interacts with glycoprotein K (gK) and its interacting partner protein UL20 (N. Jambunathan, D. Chouljenko, P. Desai, A. S. Charles, R. Subramanian, V. N. Chouljenko, and K. G. Kousoulas, J Virol 88:5927–5935, 2014, http://dx.doi.org/10.1128/JVI.00278-14), facilitating cytoplasmic virion envelopment. Alignment of UL37 homologs encoded by alphaherpesviruses revealed the presence of highly conserved residues in the central portion of the UL37 protein. A cadre of nine UL37 site-specific mutations were produced and tested for their ability to inhibit virion envelopment and infectious virus production. Complementation analysis revealed that replacement of tyrosines 474 and 480 with alanine failed to complement the UL37-null virus, while all other mutated UL37 genes complemented the virus efficiently. The recombinant virus DC474-480 constructed with tyrosines 474, 476, 477, and 480 mutated to alanine residues produced a gK-null-like phenotype characterized by the production of very small plaques and accumulation of capsids in the cytoplasm of infected cells. Recombinant viruses having either tyrosine 476 or 477 replaced with alanine produced a wild-type phenotype. Immunoprecipitation assays revealed that replacement of all four tyrosines with alanines substantially reduced the ability of gK to interact with UL37. Alignment of HSV UL37 with the human cytomegalovirus and Epstein-Barr virus UL37 homologs revealed that Y480 was conserved only for alphaherpesviruses. Collectively, these results suggest that the UL37 conserved tyrosine 480 residue plays a crucial role in interactions with gK to facilitate cytoplasmic virion envelopment and infectious virus production. IMPORTANCE The HSV-1 UL37 protein is conserved among all herpesviruses, functions in both

  3. Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors.

    PubMed

    Crosby, David C; Lei, Xiangyang; Gibbs, Charles G; Reinecke, Manfred G; Robinson, W Edward

    2015-01-01

    Human immunodeficiency virus (HIV) type I integrase (IN) active site, and viral DNA-binding residues K156 and K159 are predicted to interact both with strand transfer-selective IN inhibitors (STI), e.g. L-731,988, Elvitegravir (EVG), and the FDA-approved IN inhibitor, Raltegravir (RGV), and strand transfer non-selective inhibitors, e.g. dicaffeoyltartaric acids (DCTAs), e.g. L-chicoric acid (L-CA). To test posited roles for these two lysine residues in inhibitor action we assayed the potency of L-CA and several STI against a panel of K156 and K159 mutants. Mutagenesis of K156 conferred resistance to L-CA and mutagenesis of either K156 or K159 conferred resistance to STI indicating that the cationic charge at these two viral DNA-binding residues is important for inhibitor potency. IN K156N, a reported polymorphism associated with resistance to RGV, conferred resistance to L-CA and STI as well. To investigate the apparent preference L-CA exhibits for interactions with K156, we assayed the potency of several hybrid inhibitors containing combinations of DCTA and STI pharmacophores against recombinant IN K156A or K159A. Although K156A conferred resistance to diketo acid-branched bis-catechol hybrid inhibitors, neither K156A nor K159A conferred resistance to their monocatechol counterparts, suggesting that bis-catechol moieties direct DCTAs toward K156. In contrast, STI were more promiscuous in their interaction with K156 and K159. Taken together, the results of this study indicate that DCTAs interact with IN in a manner different than that of STI and suggest that DCTAs are an attractive candidate chemotype for development into drugs potent against STI-resistant IN.

  4. Specificity of coxsackievirus B3 interaction with human, but not murine, decay-accelerating factor: replacement of a single residue within short consensus repeat 2 prevents virus attachment.

    PubMed

    Pan, Jieyan; Zhang, Lili; Organtini, Lindsey J; Hafenstein, Susan; Bergelson, Jeffrey M

    2015-01-15

    Many coxsackievirus B (CVB) isolates bind to human decay-accelerating factor (DAF) as well as to the coxsackievirus and adenovirus receptor (CAR). However, the virus does not interact with murine DAF. To understand why CVB3 binds specifically to human DAF, we constructed a series of chimeric molecules in which specific regions of the human DAF molecule were replaced by the corresponding murine sequences. We found that replacement of human short consensus repeat 2 (SCR2) with murine SCR2 ablated virus binding to human DAF, as did deletion of human SCR2. Although replacement of human SCR4 had a partial inhibitory effect, deletion of SCR4 had no effect. Within human SCR2, replacement of serine 104 (S104) with the proline residue found in murine DAF eliminated virus binding. On the basis of the structure of the CVB3-DAF complex determined by cryo-electron microscopy, DAF S104 is in close contact with a viral capsid residue, a threonine at VP1 position 271. Replacement of this capsid residue with larger amino acids specifically eliminated virus attachment to human DAF but had no effect on attachment to CAR or replication in HeLa cells. Taken together, these results support the current model of virus-DAF interaction and point to a specific role for VP1 T271 and DAF S104 at the virus-DAF interface. The results of the present study point to a specific role for VP1 T271 and DAF S104 at the interface between CVB3 and DAF, and they demonstrate how subtle structural changes can dramatically influence virus-receptor interactions. In addition, the results support a recent pseudoatomic model of the CVB3-DAF interaction obtained by cryo-electron microscopy. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Transmembrane domain interactions and residue proline 378 are essential for proper structure, especially disulfide bond formation, in the human vitamin K-dependent gamma-glutamyl carboxylase.

    PubMed

    Tie, Jian-Ke; Zheng, Mei-Yan; Hsiao, Kuang-Ling N; Perera, Lalith; Stafford, Darrel W; Straight, David L

    2008-06-17

    We used recombinant techniques to create a two-chain form (residues 1-345 and residues 346-758) of the vitamin K-dependent gamma-glutamyl carboxylase, a glycoprotein located in the endoplasmic reticulum containing five transmembrane domains. The two-chain carboxylase had carboxylase and epoxidase activities similar to those of one-chain carboxylase. In addition, it had normal affinity for the propeptide of factor IX. We employed this molecule to investigate formation of the one disulfide bond in carboxylase, the transmembrane structure of carboxylase, and the potential interactions among the carboxylase's transmembrane domains. Our results indicate that the two peptides of the two-chain carboxylase are joined by a disulfide bond. Proline 378 is important for the structure necessary for disulfide formation. Results with the P378L carboxylase indicate that noncovalent bonds maintain the two-chain structure even when the disulfide bond is disrupted. As we had previously proposed, the fifth transmembrane domain of carboxylase is the last and only transmembrane domain in the C-terminal peptide of the two-chain carboxylase. We show that the noncovalent association between the two chains of carboxylase involves an interaction between the fifth transmembrane domain and the second transmembrane domain. Results of a homology model of transmembrane domains 2 and 5 suggest that not only do these two domains associate but that transmembrane domain 2 may interact with another transmembrane domain. This latter interaction may be mediated at least in part by a motif of glycine residues in the second transmembrane domain.

  6. Two-body potential model based on cosine series expansion for ionic materials

    SciTech Connect

    Oda, Takuji; Weber, William J.; Tanigawa, Hisashi

    2015-09-23

    There is a method to construct a two-body potential model for ionic materials with a Fourier series basis and we examine it. For this method, the coefficients of cosine basis functions are uniquely determined by solving simultaneous linear equations to minimize the sum of weighted mean square errors in energy, force and stress, where first-principles calculation results are used as the reference data. As a validation test of the method, potential models for magnesium oxide are constructed. The mean square errors appropriately converge with respect to the truncation of the cosine series. This result mathematically indicates that the constructed potential model is sufficiently close to the one that is achieved with the non-truncated Fourier series and demonstrates that this potential virtually provides minimum error from the reference data within the two-body representation. The constructed potential models work appropriately in both molecular statics and dynamics simulations, especially if a two-step correction to revise errors expected in the reference data is performed, and the models clearly outperform two existing Buckingham potential models that were tested. Moreover, the good agreement over a broad range of energies and forces with first-principles calculations should enable the prediction of materials behavior away from equilibrium conditions, such as a system under irradiation.

  7. Two-Body Approximations in the Design of Low-Energy Transfers Between Galilean Moons

    NASA Astrophysics Data System (ADS)

    Fantino, Elena; Castelli, Roberto

    Over the past two decades, the robotic exploration of the Solar System has reached the moons of the giant planets. In the case of Jupiter, a strong scientific interest towards its icy moons has motivated important space missions (e.g., ESAs' JUICE and NASA's Europa Mission). A major issue in this context is the design of efficient trajectories enabling satellite tours, i.e., visiting the several moons in succession. Concepts like the Petit Grand Tour and the Multi-Moon Orbiter have been developed to this purpose, and the literature on the subject is quite rich. The models adopted are the two-body problem (with the patched conics approximation and gravity assists) and the three-body problem (giving rise to the so-called low-energy transfers, LETs). In this contribution, we deal with the connection between two moons, Europa and Ganymede, and we investigate a two-body approximation of trajectories originating from the stable/unstable invariant manifolds of the two circular restricted three body problems, i.e., Jupiter-Ganymede and Jupiter-Europa. We develop ad-hoc algorithms to determine the intersections of the resulting elliptical arcs, and the magnitude of the maneuver at the intersections. We provide a means to perform very fast and accurate evaluations of the minimum-cost trajectories between the two moons. Eventually, we validate the methodology by comparison with numerical integrations in the three-body problem.

  8. Two-body potential model based on cosine series expansion for ionic materials

    DOE PAGES

    Oda, Takuji; Weber, William J.; Tanigawa, Hisashi

    2015-09-23

    There is a method to construct a two-body potential model for ionic materials with a Fourier series basis and we examine it. For this method, the coefficients of cosine basis functions are uniquely determined by solving simultaneous linear equations to minimize the sum of weighted mean square errors in energy, force and stress, where first-principles calculation results are used as the reference data. As a validation test of the method, potential models for magnesium oxide are constructed. The mean square errors appropriately converge with respect to the truncation of the cosine series. This result mathematically indicates that the constructed potentialmore » model is sufficiently close to the one that is achieved with the non-truncated Fourier series and demonstrates that this potential virtually provides minimum error from the reference data within the two-body representation. The constructed potential models work appropriately in both molecular statics and dynamics simulations, especially if a two-step correction to revise errors expected in the reference data is performed, and the models clearly outperform two existing Buckingham potential models that were tested. Moreover, the good agreement over a broad range of energies and forces with first-principles calculations should enable the prediction of materials behavior away from equilibrium conditions, such as a system under irradiation.« less

  9. C P -violating polarization asymmetry in charmless two-body decays of beauty baryons

    NASA Astrophysics Data System (ADS)

    He, Min; He, Xiao-Gang; Li, Guan-Nan

    2015-08-01

    Several baryons containing a heavy b-quark, the b-baryons, have been discovered. The charmless two-body decays of b-baryons can provide a new platform for C P violating studies in a similar way provided by charmless two-body decays of B-meson. There are new C P violating observables related to baryon polarization in b-baryon decays. We show that in the flavor S U (3 ) limit, there exists relations involving different combinations of the decay amplitudes compared with those in C P violating rate asymmetry. These new relations therefore provide interesting tests for the mechanism of C P violations in the standard model (SM) and flavor S U (3 ) symmetry. Such tests could complement the b-meson decay studies which hint at a better flavor S U (3 ) conservation in b-hadron decays than in kaon and hyperon decays. Future data from LHCb can provide new information about C P violation in the SM.

  10. Applications of the Kustaanheimo-Stieffel transformation of the perturbed two-body problem

    NASA Technical Reports Server (NTRS)

    Bond, V. R.

    1973-01-01

    The Newtonian differential equations of motion for the two-body problem can be transformed into four linear harmonic-oscillator equations by simultaneously applying the regularization step dt/ds = r and the Kustaanheimo-Stieffel (KS) transformation. The regularization step changes the independent variable from time to a new variable s, and the KS transformation transforms the position and velocity vectors from Cartesian space into a four-dimensional space. A derivation of a uniform, regular solution for the perturbed two-body problem in the four-dimensional space is presented. The variation-of-parameters technique is used to develop expressions for the derivatives of ten elements (which are constants in the unperturbed motion) for the general case that includes both perturbations which can arise from a potential and perturbations which cannot be derived from a potential. This ten-element solution has mixed secular terms that degrade the long-term accuracy during numerical integration. Therefore, to eliminate these terms, the solution is modified by introducing two additional elements.

  11. Applications of the Kustaanheimo-Stieffel transformation of the perturbed two-body problem

    NASA Technical Reports Server (NTRS)

    Bond, V. R.

    1973-01-01

    The Newtonian differential equations of motion for the two-body problem can be transformed into four linear harmonic-oscillator equations by simultaneously applying the regularization step dt/ds = r and the Kustaanheimo-Stieffel (KS) transformation. The regularization step changes the independent variable from time to a new variable s, and the KS transformation transforms the position and velocity vectors from Cartesian space into a four-dimensional space. A derivation of a uniform, regular solution for the perturbed two-body problem in the four-dimensional space is presented. The variation-of-parameters technique is used to develop expressions for the derivatives of ten elements (which are constants in the unperturbed motion) for the general case that includes both perturbations which can arise from a potential and perturbations which cannot be derived from a potential. This ten-element solution has mixed secular terms that degrade the long-term accuracy during numerical integration. Therefore, to eliminate these terms, the solution is modified by introducing two additional elements.

  12. Non-singular orbital elements for special perturbations in the two-body problem

    NASA Astrophysics Data System (ADS)

    Baù, Giulio; Bombardelli, Claudio; Peláez, Jesús; Lorenzini, Enrico

    2015-12-01

    Seven spatial elements and a time element are proposed as the state variables of a new special perturbation method for the two-body problem. The new elements hold for zero eccentricity and inclination and for negative values of the total energy. They are developed by combining a spatial transformation into projective coordinates (as in the Burdet-Ferrándiz regularization) with a time transformation in which the exponent of the orbital radius is equal to one instead of two (as commonly done in the literature). By following this approach, we discover a new linearization of the two-body problem, from which the orbital elements can be generated by the variation of parameters method. The geometrical significance of the spatial quantities is revealed by a new intermediate frame which differs from a local vertical local horizontal frame by one rotation in the instantaneous orbital plane. Four elements parametrize the attitude in space of this frame, which in turn defines the orientation of the orbital plane and fixes the departure direction for the longitude of the propagated body. The remaining three elements determine the motion along the radial unit vector and the orbital longitude. The performance of the method, tested using a series of benchmark orbit propagation scenarios, is extremely good when compared to several regularized formulations, some of which have been modified and improved here for the first time.

  13. A new set of integrals of motion to propagate the perturbed two-body problem

    NASA Astrophysics Data System (ADS)

    Baù, Giulio; Bombardelli, Claudio; Peláez, Jesús

    2013-05-01

    A formulation of the perturbed two-body problem that relies on a new set of orbital elements is presented. The proposed method represents a generalization of the special perturbation method published by Peláez et al. (Celest Mech Dyn Astron 97(2):131-150, 2007) for the case of a perturbing force that is partially or totally derivable from a potential. We accomplish this result by employing a generalized Sundman time transformation in the framework of the projective decomposition, which is a known approach for transforming the two-body problem into a set of linear and regular differential equations of motion. Numerical tests, carried out with examples extensively used in the literature, show the remarkable improvement of the performance of the new method for different kinds of perturbations and eccentricities. In particular, one notable result is that the quadratic dependence of the position error on the time-like argument exhibited by Peláez's method for near-circular motion under the J2 perturbation is transformed into linear. Moreover, the method reveals to be competitive with two very popular element methods derived from the Kustaanheimo-Stiefel and Sperling-Burdet regularizations.

  14. The interaction between natural organic matter in raw waters and pesticide residues: a three dimensional excitation-emission matrix (3DEEM) fluorescence investigation.

    PubMed

    Beale, David J; Porter, Nichola A; Roddick, Felicity A

    2013-01-01

    This paper examines the interaction between dissolved natural organic matter and pesticide residues, both of which are found in raw water sources, using three dimensional excitation-emission matrix (3DEEM) fluorescence spectroscopy. It was observed that pesticide residue at 0.1 mg L(-1) formed a complex with humic-like fluorophores that are commonly found in raw water samples. Applying 3DEEM fluorescence to investigate the humic fractions, it was found that identification of changes in water sources was possible, and, importantly, the presence of a number of pesticides was able to be determined. In addition, the formation of this complex, and the influence of soluble cations and anions upon it, was shown to impact the efficiency of analytical extraction procedures for pesticides; however, 3DEEM fluorescence could be an approach to account for such losses.

  15. Probing the acidic residue within the integrin binding site of laminin-511 that interacts with the metal ion-dependent adhesion site of α6β1 integrin.

    PubMed

    Taniguchi, Yukimasa; Li, Shaoliang; Takizawa, Mamoru; Oonishi, Eriko; Toga, Junko; Yagi, Emiko; Sekiguchi, Kiyotoshi

    2017-06-03

    Laminins are major cell-adhesive proteins of basement membranes that interact with integrins in a divalent cation-dependent manner. Laminin-511 consists of α5, β1, and γ1 chains, of which three laminin globular domains of the α5 chain (α5/LG1-3) and a Glu residue in the C-terminal tail of chain γ1 (γ1-Glu1607) are required for binding to integrins. However, it remains unsettled whether the Glu residue in the γ1 tail is involved in integrin binding by coordinating the metal ion in the metal ion-dependent adhesion site of β1 integrin (β1-MIDAS), or by stabilizing the conformation of α5/LG1-3. To address this issue, we examined whether α5/LG1-3 contain an acidic residue required for integrin binding that is as critical as the Glu residue in the γ1 tail; to achieve this, we undertook exhaustive alanine substitutions of the 54 acidic residues present in α5/LG1-3 of the E8 fragment of laminin-511 (LM511E8). Most of the alanine mutants possessed α6β1 integrin binding activities comparable with wild-type LM511E8. Alanine substitution for α5-Asp3198 and Asp3219 caused mild reduction in integrin binding activity, and that for α5-Asp3218 caused severe reduction, possibly resulting from conformational perturbation of α5/LG1-3. When α5-Asp3218 was substituted with asparagine, the resulting mutant possessed significant binding activity to α6β1 integrin, indicating that α5-Asp3218 is not directly involved in integrin binding through coordination with the metal ion in β1-MIDAS. Given that substitution of γ1-Glu1607 with glutamine nullified the binding activity to α6β1 integrin, these results, taken together, support the possibility that the critical acidic residue coordinating the metal ion in β1-MIDAS is Glu1607 in the γ1 tail, but no such residue is present in α5/LG1-3. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis.

    PubMed

    Xue, Weiwei; Jin, Xiaojie; Ning, Lulu; Wang, Meixia; Liu, Huanxiang; Yao, Xiaojun

    2013-01-28

    The rapid emergence of cross-resistance to the integrase strand transfer inhibitors (INSTIs) has become a serious problem in the therapy of human immunodeficiency virus type 1 (HIV-1) infection. Understanding the detailed molecular mechanism of INSTIs cross-resistance is therefore critical for the development of new effective therapy against cross-resistance. On the basis of the homology modeling constructed structure of tetrameric HIV-1 intasome, the detailed molecular mechanism of the cross-resistance mutation E138K/Q148K to three important INSTIs (Raltegravir (RAL, FDA approved in 2007), Elvitegravir (EVG, FDA approved in 2012), and Dolutegravir (DTG, phase III clinical trials)) was investigated by using molecular dynamics (MD) simulation and residue interaction network (RIN) analysis. The results from conformation analysis and binding free energy calculation can provide some useful information about the detailed binding mode and cross-resistance mechanism for the three INSTIs to HIV-1 intasome. Binding free energy decomposition analysis revealed that Pro145 residue in the 140s 1oop (Gly140 to Gly149) of the HIV-1 intasome had strong hydrophobic interactions with INSTIs and played an important role in the binding of INSTIs to HIV-1 intasome active site. A systematic comparison and analysis of the RIN proves that the communications between the residues in the resistance mutant is increased when compared with that of the wild-type HIV-1 intasome. Further analysis indicates that residue Pro145 may play an important role and is relevant to the structure rearrangement in HIV-1 intasome active site. In addition, the chelating ability of the oxygen atoms in INSTIs (e.g., RAL and EVG) to Mg(2+) in the active site of the mutated intasome was reduced due to this conformational change and is also responsible for the cross-resistance mechanism. Notably, the cross-resistance mechanism we proposed could give some important information for the future rational design of novel

  17. Molecular modeling and residue interaction network studies on the mechanism of binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598.

    PubMed

    Xue, Weiwei; Jiao, Pingzu; Liu, Huanxiang; Yao, Xiaojun

    2014-04-01

    Hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase (RdRp) with essential functions in viral genome replication and represents a promising therapeutic target to develop direct-acting antivirals (DAAs). Multiple nonnucleoside inhibitors (NNIs) binding sites have been identified within the polymerase. VX-222 and ANA598 are two NNIs targeting thumb II site and palm I site of HCV NS5B polymerase, respectively. These two molecules have been shown to be very effective in phase II clinical trials. However, the emergence of resistant HCV replicon variants (L419M, M423T, I482L mutants to VX-222 and M414T, M414L, G554D mutants to ANA598) has significantly decreased their efficacy. To elucidate the molecular mechanism about how these mutations influenced the drug binding mode and decreased drug efficacy, we studied the binding modes of VX-222 and ANA598 to wild-type and mutant polymerase by molecular modeling approach. Molecular dynamics (MD) simulations results combined with binding free energy calculations indicated that the mutations significantly altered the binding free energy and the interaction for the drugs to polymerase. The further per-residue binding free energy decomposition analysis revealed that the mutations decreased the interactions with several key residues, such as L419, M423, L474, S476, I482, L497, for VX-222 and L384, N411, M414, Y415, Q446, S556, G557 for ANA598. These were the major origins for the resistance to these two drugs. In addition, by analyzing the residue interaction network (RIN) of the complexes between the drugs with wild-type and the mutant polymerase, we found that the mutation residues in the networks involved in the drug resistance possessed a relatively lower size of topology centralities. The shift of betweenness and closeness values of binding site residues in the mutant polymerase is relevant to the mechanism of drug resistance of VX-222 and ANA598. These results can provide an atomic-level understanding about

  18. Role of the Tryptophan Residues in the Specific Interaction of the Sea Anemone Stichodactyla helianthus's Actinoporin Sticholysin II with Biological Membranes.

    PubMed

    García-Linares, Sara; Maula, Terhi; Rivera-de-Torre, Esperanza; Gavilanes, José G; Slotte, J Peter; Martínez-Del-Pozo, Álvaro

    2016-11-22

    Actinoporins are pore-forming toxins from sea anemones. Upon interaction with sphingomyelin-containing bilayers, they become integral oligomeric membrane structures that form a pore. Sticholysin II from Stichodactyla helianthus contains five tryptophans located at strategic positions; its role has now been studied using different mutants. Results show that W43 and W115 play a determinant role in maintaining the high thermostability of the protein, while W146 provides specific interactions for protomer-protomer assembly. W110 and W114 sustain the hydrophobic effect, which is one of the major driving forces for membrane binding in the presence of Chol. However, in its absence, additional interactions with sphingomyelin are required. These conclusions were confirmed with two sphingomyelin analogues, one of which had impaired hydrogen bonding properties. The results obtained support actinoporins' Trp residues playing a major role in membrane recognition and binding, but their residues have an only minor influence on the diffusion and oligomerization steps needed to assemble a functional pore.

  19. Developing an Acidic Residue Reactive and Sulfoxide-Containing MS-Cleavable Homobifunctional Cross-Linker for Probing Protein–Protein Interactions

    PubMed Central

    2016-01-01

    Cross-linking mass spectrometry (XL-MS) has become a powerful strategy for defining protein–protein interactions and elucidating architectures of large protein complexes. However, one of the inherent challenges in MS analysis of cross-linked peptides is their unambiguous identification. To facilitate this process, we have previously developed a series of amine-reactive sulfoxide-containing MS-cleavable cross-linkers. These MS-cleavable reagents have allowed us to establish a common robust XL-MS workflow that enables fast and accurate identification of cross-linked peptides using multistage tandem mass spectrometry (MSn). Although amine-reactive reagents targeting lysine residues have been successful, it remains difficult to characterize protein interaction interfaces with little or no lysine residues. To expand the coverage of protein interaction regions, we present here the development of a new acidic residue-targeting sulfoxide-containing MS-cleavable homobifunctional cross-linker, dihydrazide sulfoxide (DHSO). We demonstrate that DHSO cross-linked peptides display the same predictable and characteristic fragmentation pattern during collision induced dissociation as amine-reactive sulfoxide-containing MS-cleavable cross-linked peptides, thus permitting their simplified analysis and unambiguous identification by MSn. Additionally, we show that DHSO can provide complementary data to amine-reactive reagents. Collectively, this work not only enlarges the range of the application of XL-MS approaches but also further demonstrates the robustness and applicability of sulfoxide-based MS-cleavability in conjunction with various cross-linking chemistries. PMID:27417384

  20. Interaction of the pertussis toxin peptide containing residues 30-42 with DR1 and the T-cell receptors of 12 human T-cell clones.

    PubMed Central

    De Magistris, M T; Di Tommaso, A; Domenighini, M; Censini, S; Tagliabue, A; Oksenberg, J R; Steinman, L; Judd, A K; O'Sullivan, D; Rappuoli, R

    1992-01-01

    The interaction of the immunodominant pertussis toxin peptide containing residues 30-42 (p30-42) with soluble DR1 molecules and the T-cell receptor (TCR) of 12 DR1-restricted human T-cell clones has been analyzed. Peptide analogues of p30-42 containing single alanine substitutions were used in DR1-binding and T-cell proliferation assays to identify the major histocompatibility complex and TCR contact residues. Each T-cell clone was found to recognize p30-42 with a different fine specificity. However, a common core comprising amino acids 33-39 was found to be important for stimulation of all T-cell clones. Within this core two residues, Leu33 and Leu36, interact with the DR1 molecule, whereas Asp34, His35, Thr37, and Arg39 are important for TCR recognition in most of the clones. Computer modeling of the structure of p30-42 showed that an alpha-helical conformation is compatible with the experimental data. The analysis of TCR rearrangement revealed that the peptide was recognized by T-cell clones expressing different variable region alpha (V alpha) and variable region beta (V beta) chains, although a preferential use of V alpha 8-V beta 13 and V alpha 11-V beta 18 combinations was found in clones from the same donor. Understanding the details of the interaction of antigenic peptides with the major histocompatibility complex and TCR molecules should provide the theoretical basis to design T-cell epitopes and obtain more immunogenic vaccines. Images PMID:1313575

  1. The Same Periplasmic ExbD Residues Mediate In Vivo Interactions between ExbD Homodimers and ExbD-TonB Heterodimers ▿ †

    PubMed Central

    Ollis, Anne A.; Postle, Kathleen

    2011-01-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD2) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD2 assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD2-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic. PMID:21984795

  2. The same periplasmic ExbD residues mediate in vivo interactions between ExbD homodimers and ExbD-TonB heterodimers.

    PubMed

    Ollis, Anne A; Postle, Kathleen

    2011-12-01

    The TonB system couples cytoplasmic membrane proton motive force to TonB-gated outer membrane transporters for active transport of nutrients into the periplasm. In Escherichia coli, cytoplasmic membrane proteins ExbB and ExbD promote conformational changes in TonB, which transmits this energy to the transporters. The only known energy-dependent interaction occurs between the periplasmic domains of TonB and ExbD. This study identified sites of in vivo homodimeric interactions within ExbD periplasmic domain residues 92 to 121. ExbD was active as a homodimer (ExbD(2)) but not through all Cys substitution sites, suggesting the existence of conformationally dynamic regions in the ExbD periplasmic domain. A subset of homodimeric interactions could not be modeled on the nuclear magnetic resonance (NMR) structure without significant distortion. Most importantly, the majority of ExbD Cys substitutions that mediated homodimer formation also mediated ExbD-TonB heterodimer formation with TonB A150C. Consistent with the implied competition, ExbD homodimer formation increased in the absence of TonB. Although ExbD D25 was not required for their formation, ExbD dimers interacted in vivo with ExbB. ExbD-TonB interactions required ExbD transmembrane domain residue D25. These results suggested a model where ExbD(2) assembled with ExbB undergoes a transmembrane domain-dependent transition and exchanges partners in localized homodimeric interfaces to form an ExbD(2)-TonB heterotrimer. The findings here were also consistent with our previous hypothesis that ExbD guides the conformation of the TonB periplasmic domain, which itself is conformationally dynamic.

  3. Entropy theorems in classical mechanics, general relativity, and the gravitational two-body problem

    NASA Astrophysics Data System (ADS)

    Oltean, Marius; Bonetti, Luca; Spallicci, Alessandro D. A. M.; Sopuerta, Carlos F.

    2016-09-01

    In classical Hamiltonian theories, entropy may be understood either as a statistical property of canonical systems or as a mechanical property, that is, as a monotonic function of the phase space along trajectories. In classical mechanics, there are theorems which have been proposed for proving the nonexistence of entropy in the latter sense. We explicate, clarify, and extend the proofs of these theorems to some standard matter (scalar and electromagnetic) field theories in curved spacetime, and then we show why these proofs fail in general relativity; due to properties of the gravitational Hamiltonian and phase space measures, the second law of thermodynamics holds. As a concrete application, we focus on the consequences of these results for the gravitational two-body problem, and in particular, we prove the noncompactness of the phase space of perturbed Schwarzschild-Droste spacetimes. We thus identify the lack of recurring orbits in phase space as a distinct sign of dissipation and hence entropy production.

  4. Qualitative analysis of the anisotropic two-body problem with relativistic potential

    NASA Astrophysics Data System (ADS)

    Paşca, Daniel; Valls, Cláudia

    2013-06-01

    In this paper we study the two-body problem that describes the motion of two-point masses in an anisotropic space under the influence of a Newtonian force-law with two relativistic correction terms. We will show that the set of initial conditions leading to collisions and ejections have positive measure and study the capture and escape solutions in the zero-energy case using the infinity manifold. We will also apply the Melnikov method to show that the flow on the zero-energy manifold of another potential which is the sum of the classical Keplerian potential and two anisotropic perturbation which also take into account two relativistic correction terms is chaotic.

  5. Treatment of the two-body Coulomb problem as a short-range potential

    NASA Astrophysics Data System (ADS)

    Gasaneo, G.; Ancarani, L. U.

    2009-12-01

    The scattering wave function and the transition amplitude for the two-body Coulomb problem are written as power series of the Sommerfeld parameter. Making use of a mathematical study of the nth derivatives of Kummer function with respect to its first parameter, the series coefficients are expressed analytically in terms of multivariable hypergeometric functions. We establish the connection with the Born series based on the free particle Green’s function and show its applicability to long-range potentials. We also relate our analysis to recent works on the distorted-wave theory for the Coulomb problem. For the transition amplitude, the Born series is presented and compared to the series obtained from the exact well-known Rutherford result. Since the two series differ, care must be taken when extracting the relevant information about the scattering. Finally, implications for three-body problems are discussed.

  6. Opposite charged two-body system of identical counterrotating black holes

    NASA Astrophysics Data System (ADS)

    Cabrera-Munguia, I.; Lämmerzahl, Claus; López, L. A.; Macías, Alfredo

    2013-10-01

    A four-parametric exact solution describing a two-body system of identical Kerr-Newman counterrotating black holes endowed with opposite electric/magnetic charges is presented. The axis conditions are solved in order to really describe two black holes separated by a massless strut. Moreover, the explicit form of the horizon half length parameter σ in terms of physical Komar parameters, i.e., Komar’s mass M, electric charge QE, angular momentum J, and a coordinate distance R is derived. Additionally, magnetic charges QB arise from the rotation of electrically charged black holes. As a consequence, in order to account for the contribution to the mass of the magnetic charge, the usual Smarr mass formula should be generalized, as it is proposed by A. Tomimatsu, Prog. Theor. Phys. 72, 73 (1984).

  7. Evidence for the two-body charmless baryonic decay {B}+\\to p\\overline{Λ}

    NASA Astrophysics Data System (ADS)

    Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Romeu, J. Arnau; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baszczyk, M.; Batozskaya, V.; Batsukh, B.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Bel, L. J.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Bird, T.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britsch, M.; Britton, T.; Brodzicka, J.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Gomez, M. Calvo; Camboni, A.; Campana, P.; Perez, D. H. Campora; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cavallero, G.; Cenci, R.; Chamont, D.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chobanova, V.; Chrzaszcz, M.; Vidal, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collazuol, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Sobral, C. M. Costa; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Torres, M. Cruz; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Aguiar Francisco, O.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C.-T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Suárez, A. Dosil; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dungs, K.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Déléage, N.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fay, R.; Fazzini, D.; Ferguson, D.; Prieto, A. Fernandez; Ferrari, F.; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Lima, V. Franco; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Torreira, A. Gallas; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Martin, L. M. Garcia; Pardiñas, J. García; Tico, J. Garra; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gian`ı, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Gándara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Griffith, P.; Grillo, L.; Cazon, B. R. Gruberg; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hatch, M.; He, J.; Head, T.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, H.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hussain, N.; Hutchcroft, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Koliiev, S.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Kosmyntseva, A.; Kozachuk, A.; Kozeiha, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Cid, E. Lemos; Leroy, O.; Lesiak, T.; Leverington, B.; Li, T.; Li, Y.; Likhomanenko, T.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Martinez, M. Lucio; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Maratas, J.; Marchand, J. F.; Marconi, U.; Benito, C. Marin; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Santos, D. Martinez; Vidal, F. Martinez; Tostes, D. Martins; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Meissner, M.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Minard, M.-N.; Mitzel, D. S.; Mogini, A.; Rodriguez, J. Molina; Monroy, I. A.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Mussini, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Goicochea, J. M. Otalora; Otto, A.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, G. D.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Altarelli, M. Pepe; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Olloqui, E. Picatoste; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Casasus, M. Plo; Poikela, T.; Polci, F.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Popov, A.; Popov, D.; Popovici, B.; Poslavskii, S.; Potterat, C.; Price, E.; Price, J. D.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Pernas, M. Ramos; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Redi, F.; Reichert, S.; dos Reis, A. C.; Alepuz, C. Remon; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Molina, V. Rives; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Lopez, J. A. Rodriguez; Perez, P. Rodriguez; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Vidal, A. Romero; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Valls, P. Ruiz; Silva, J. J. Saborido; Sadykhov, E.; Sagidova, N.; Saitta, B.; Guimaraes, V. Salustino; Mayordomo, C. Sanchez; Sedes, B. Sanmartin; Santacesaria, R.; Rios, C. Santamarina; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schubert, K.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Coutinho, R. Silva; de Oliveira, L. Silva; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Snoek, H.; Lavra, l. Soares; Sokoloff, M. D.; Soler, F. J. P.; De Paula, B. Souza; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Toriello, F.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vallier, A.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Vernet, M.; Vesterinen, M.; Viaud, B.; Vieira, D.; Diaz, M. Vieites; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Sierra, C. Vázquez; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zucchelli, S.

    2017-04-01

    A search for the rare two-body charmless baryonic decay {B}+\\to p\\overline{Λ} is performed with pp collision data, corresponding to an integrated luminosity of 3 fb-1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. An excess of {B}+\\to p\\overline{Λ} candidates with respect to background expectations is seen with a statistical significance of 4.1 standard deviations, and constitutes the first evidence for this decay. The branching fraction, measured using the B + → K S 0 π + decay for normalisation, is {B}({B}+\\to p\\overline{Λ})=(2.{4}_{-0.8}^{+1.0}± 0.3)× 1{0}^{-7}, where the first uncertainty is statistical and the second systematic. [Figure not available: see fulltext.

  8. First results with charmless two-body B-decays at LHCb, and future prospects

    ScienceCinema

    None

    2016-07-12

    LHCb is an experiment which is designed to perform flavour physics measurements at the LHC. Charged two-body charmless B decays (e.g. B^0 -> Kpi, pipi, B_s->KK, etc) receive significant contributions from loop diagrams and are thus sensitive probes of New Physics. Study of these modes is therefore an important physics goal of LHCb. First results will be presented, using around 37 pb^{-1} of data collected at \\sqrt{s}=7 TeV in 2010. These results illustrate the power of the LHCb trigger system and particle identification capabilities of the RICH detectors in isolating clean samples of each final state, and include preliminary measurements of direct CP-violation in certain key modes. The prospects for these measurements in the coming run will be presented. A brief survey will also be given of results and prospect in other areas of the LHCb physics programme.

  9. The structure and dynamics of silica polymorphs using a two-body effective potential model

    NASA Astrophysics Data System (ADS)

    Tse, John S.; Klug, Dennis D.

    1991-12-01

    The performance of a recently proposed two-body potential model for SiO2 [van Beest et al., Phys. Rev. Lett. 64, 1995 (1990)] was critically evaluated through the calculation of the static and dynamical properties of several polymorphs of SiO2 using molecular dynamics methods. It was found that the calculated static structures are in excellent agreement with experiments. In particular, the pressure-volume equations of state for α-quartz, cristobalite, and stishovite, the pressure-induced amorphization transformation in α-quartz and thermally induced the α→β transformation in cristobalite are well reproduced by this model. The calculated vibrational spectra are in fair agreement with experiments. The strengths and the weaknesses of the potential will be presented and discussed.

  10. Parametric study of two-body floating-point wave absorber

    NASA Astrophysics Data System (ADS)

    Amiri, Atena; Panahi, Roozbeh; Radfar, Soheil

    2016-03-01

    In this paper, we present a comprehensive numerical simulation of a point wave absorber in deep water. Analyses are performed in both the frequency and time domains. The converter is a two-body floating-point absorber (FPA) with one degree of freedom in the heave direction. Its two parts are connected by a linear mass-spring-damper system. The commercial ANSYS-AQWA software used in this study performs well in considering validations. The velocity potential is obtained by assuming incompressible and irrotational flow. As such, we investigated the effects of wave characteristics on energy conversion and device efficiency, including wave height and wave period, as well as the device diameter, draft, geometry, and damping coefficient. To validate the model, we compared our numerical results with those from similar experiments. Our study results can clearly help to maximize the converter's efficiency when considering specific conditions.

  11. Medium modified two-body scattering amplitude from proton-nucleus total cross-sections

    NASA Astrophysics Data System (ADS)

    Tripathi, R. K.; Wilson, J. W.; Cucinotta, F. A.

    2001-02-01

    Recently (R.K. Tripathi, J.W. Wilson, F.A. Cucinotta, Nucl. Instr. and Meth. B 145 (1998) 277; R.K. Tripathi, F.A. Cucinotta, J.W. Wilson, NASA-TP-1998-208438), we have extracted nucleon-nucleon (N-N) cross-sections in the medium directly from experiment. The in-medium N-N cross-sections form the basic ingredients of several heavy-ion scattering approaches including the coupled-channel approach developed at the NASA Langley Research Center. Here, we investigate the ratio of real to imaginary part of the two-body scattering amplitude in the medium. These ratios are used in combination with the in-medium N-N cross-sections to calculate total proton-nucleus cross-sections. The agreement is excellent with the available experimental data. These cross-sections are needed for the radiation risk assessment of space missions.

  12. First results with charmless two-body B-decays at LHCb, and future prospects

    SciTech Connect

    2011-02-22

    LHCb is an experiment which is designed to perform flavour physics measurements at the LHC. Charged two-body charmless B decays (e.g. B^0 -> Kpi, pipi, B_s->KK, etc) receive significant contributions from loop diagrams and are thus sensitive probes of New Physics. Study of these modes is therefore an important physics goal of LHCb. First results will be presented, using around 37 pb^{-1} of data collected at \\sqrt{s}=7 TeV in 2010. These results illustrate the power of the LHCb trigger system and particle identification capabilities of the RICH detectors in isolating clean samples of each final state, and include preliminary measurements of direct CP-violation in certain key modes. The prospects for these measurements in the coming run will be presented. A brief survey will also be given of results and prospect in other areas of the LHCb physics programme.

  13. Measurements of Charmless Three-Body and Quasi-Two-Body B Decays

    SciTech Connect

    Barrera, Barbara

    2000-08-28

    The authors present preliminary results of a search for several exclusive charmless hadronic B decays from electron-positron annihilation data collected by the BaBar detector near the Upsilon(4S) resonance. These include three-body decay modes with final states h{+-}h{sup minus-plus}h{+-} and h{+-}h{sup minus-plus}pi{sup 0}, and quasi-two-body decay modes with final states X{sup 0}h and X{sup 0}K{sub S}{sup 0}, where h = pi or K and X{sup 0} = eta-prime or omega. They find beta(B{sup 0} --> rho{sup minus-plus}pi{sup {+-}}) = (49{+-}13{sub {minus}5}{sup +6}) x 10{sup {minus}6} and beta(B{sup +} --> eta-prime-K{sup +}) = (62{+-}18{+-}8) x 10{sup {minus}6} and present upper limits for right other decays.

  14. Proton-Nucleus Elastic Cross Sections Using Two-Body In-Medium Scattering Amplitudes

    NASA Technical Reports Server (NTRS)

    Tripathi, R. K.; Wilson, John W.; Cucinotta, Francis A.

    2001-01-01

    Recently, a method was developed of extracting nucleon-nucleon (NN) cross sections in the medium directly from experiment. The in-medium NN cross sections form the basic ingredients of several heavy-ion scattering approaches including the coupled-channel approach developed at the Langley Research Center. The ratio of the real to the imaginary part of the two-body scattering amplitude in the medium was investigated. These ratios are used in combination with the in-medium NN cross sections to calculate elastic proton-nucleus cross sections. The agreement is excellent with the available experimental data. These cross sections are needed for the radiation risk assessment of space missions.

  15. Energy spectra of massive two-body decay products and mass measurement

    NASA Astrophysics Data System (ADS)

    Agashe, Kaustubh; Franceschini, Roberto; Hong, Sungwoo; Kim, Doojin

    2016-04-01

    We have recently established a new method for measuring the mass of unstable particles produced at hadron colliders based on the analysis of the energy distribution of a mass less product from their two-body decays. The central ingredient of our proposal is the remarkable result that, for an unpolarized decaying particle, the location of the peak in the energy distribution of the observed decay product is identical to the (fixed) value of the energy that this particle would have in the rest-frame of the decaying particle, which, in turn, is a simple function of the involved masses. In addition, we utilized the property that this energy distribution is symmetric around the location of peak when energy is plotted on a logarithmic scale. The general strategy was demonstrated in several specific cases, including both beyond the standard model particles, as well as for the top quark. In the present work, we generalize this method to the case of a massive decay product from a two-body decay; this procedure is far from trivial because (in general) both the above-mentioned properties are no longer valid. Nonetheless, we propose a suitably modified parametrization of the energy distribution that was used successfully for the massless case, which can deal with the massive case as well. We test this parametrization on concrete examples of energy spectra of Z bosons from the decay of a heavier supersymmetric partner of top quark (stop) into a Z boson and a lighter stop. After establishing the accuracy of this parametrization, we study a realistic application for the same process, but now including dominant backgrounds and using foreseeable statistics at LHC14, in order to determine the performance of this method for an actual mass measurement. The upshot of our present and previous work is that, in spite of energy being a Lorentz-variant quantity, its distribution emerges as a powerful tool for mass measurement at hadron colliders.

  16. Energy spectra of massive two-body decay products and mass measurement

    DOE PAGES

    Agashe, Kaustubh; Franceschini, Roberto; Hong, Sungwoo; ...

    2016-04-26

    Here, we have recently established a new method for measuring the mass of unstable particles produced at hadron colliders based on the analysis of the energy distribution of a massless product from their two-body decays. The central ingredient of our proposal is the remarkable result that, for an unpolarized decaying particle, the location of the peak in the energy distribution of the observed decay product is identical to the (fixed) value of the energy that this particle would have in the rest-frame of the decaying particle, which, in turn, is a simple function of the involved masses. In addition, wemore » utilized the property that this energy distribution is symmetric around the location of peak when energy is plotted on a logarithmic scale. The general strategy was demonstrated in several specific cases, including both beyond the standard model particles, as well as for the top quark. In the present work, we generalize this method to the case of a massive decay product from a two-body decay; this procedure is far from trivial because (in general) both the above-mentioned properties are no longer valid. Nonetheless, we propose a suitably modified parametrization of the energy distribution that was used successfully for the massless case, which can deal with the massive case as well. We test this parametrization on concrete examples of energy spectra of Z bosons from the decay of a heavier supersymmetric partner of top quark (stop) into a Z boson and a lighter stop. After establishing the accuracy of this parametrization, we study a realistic application for the same process, but now including dominant backgrounds and using foreseeable statistics at LHC14, in order to determine the performance of this method for an actual mass measurement. The upshot of our present and previous work is that, in spite of energy being a Lorentz-variant quantity, its distribution emerges as a powerful tool for mass measurement at hadron colliders.« less

  17. Energy spectra of massive two-body decay products and mass measurement

    SciTech Connect

    Agashe, Kaustubh; Franceschini, Roberto; Hong, Sungwoo; Kim, Doojin

    2016-04-26

    Here, we have recently established a new method for measuring the mass of unstable particles produced at hadron colliders based on the analysis of the energy distribution of a massless product from their two-body decays. The central ingredient of our proposal is the remarkable result that, for an unpolarized decaying particle, the location of the peak in the energy distribution of the observed decay product is identical to the (fixed) value of the energy that this particle would have in the rest-frame of the decaying particle, which, in turn, is a simple function of the involved masses. In addition, we utilized the property that this energy distribution is symmetric around the location of peak when energy is plotted on a logarithmic scale. The general strategy was demonstrated in several specific cases, including both beyond the standard model particles, as well as for the top quark. In the present work, we generalize this method to the case of a massive decay product from a two-body decay; this procedure is far from trivial because (in general) both the above-mentioned properties are no longer valid. Nonetheless, we propose a suitably modified parametrization of the energy distribution that was used successfully for the massless case, which can deal with the massive case as well. We test this parametrization on concrete examples of energy spectra of Z bosons from the decay of a heavier supersymmetric partner of top quark (stop) into a Z boson and a lighter stop. After establishing the accuracy of this parametrization, we study a realistic application for the same process, but now including dominant backgrounds and using foreseeable statistics at LHC14, in order to determine the performance of this method for an actual mass measurement. The upshot of our present and previous work is that, in spite of energy being a Lorentz-variant quantity, its distribution emerges as a powerful tool for mass measurement at hadron colliders.

  18. Two-body wear of dental porcelain and substructure oxide ceramics.

    PubMed

    Rosentritt, Martin; Preis, Verena; Behr, Michael; Hahnel, Sebastian; Handel, Gerhard; Kolbeck, Carola

    2012-06-01

    The aim of this in vitro study was to investigate the two-body wear of different ceramics. Two-body wear tests were performed in a chewing simulator with steatite and enamel antagonists, respectively. Specimens were loaded in a pin-on-block design with a vertical load of 50 N for 1.2 × 10(5) cycles; (f = 1.6 Hz; lateral movement, 1 mm; mouth opening: 2 mm). Human enamel was used as a reference. Three zirconia ceramics, three veneering porcelains, two glass-infiltrated and one lithium disilicate ceramic were investigated. Veneering and lithium disilicate ceramics were glazed before testing. Surface roughness Ra (SP6, Perthen-Feinprüf, G) and wear depth were determined using a 3D scanner (Laserscan 3D, Willytec, G). SEM (Quanta FEG 400, FEI, USA) pictures of the worn specimens and antagonists were made for evaluating wear performance. Veneering porcelain provided wear traces between 71.2 and 124.1 μm (enamel antagonist) and 117.4 and 274.1 μm (steatite). Wear of the steatite antagonists varied between 0.618 and 2.85 mm². No wear was found for zirconia and glass-infiltrated substructure ceramics. Also, no wear was found for the corresponding antagonists. Wear of specimens and antagonists was strongly material dependent. No visible wear was found on zirconia and glass-infiltrated ceramics. Porcelain and lithium disilicate ceramic showed a comparable or lower wear than the enamel reference. Antagonist wear was found to be lower when specimens were made of substructure oxide ceramics instead of veneering porcelain. From the point of wear testing, zirconia may be used for the fabrication of fixed dental prosthesis without veneering.

  19. a Study of the Charged Two-Body Decays of the Neutral D Mesons

    NASA Astrophysics Data System (ADS)

    Peng, Kuang-Chung (K. C.).

    1995-01-01

    The charged two-body decays of D^0 mesons produced by 500 GeV/c pi -incident on platium and carbon foil targets at the Fermilab Tagged Particle Laboratory have been analyzed. Three measurements are presented in this thesis: (1) Branching Ratios of Charged Two-body Decays: {Gamma(D^0to K^+K^-)overGamma(D^0to K^-pi^+)}= 0.107+/-0.003 +/-0.003, {Gamma(D^0to pi^+pi^-)over Gamma(D ^0to K^-pi^+)} =0.040 +/-0.002+/-0.002, {Gamma(D^0 to K^+K^-)overGamma(D^0 topi^+pi^-)}=2.65+/-0.14 +/-0.13, and {Gamma(D^0 to K^-pi^-pi^+pi ^+)overGamma(D^0to K^ -pi^+)} =2.19+/-.0.3+/-.0.08; (2) Lifetime Difference: tau_ {KK}=0.414+/-0.012+/-0.014, tau _{Kpi}=0.409+/-0.003+/-0.004, with Deltagamma= {-}0.06 +/-0.15+/-0.15, or the upper limit of Mixing rate as {cal R}_sp {rm mix}{it y}<0.00079 (due to lifetime difference only) at mix 90% confidence level; and (3) CP Asymmetry Parameters: A_sp{CP}{BR}(K^+/- K^mp) = {-}0.018+/-0.054+/-0.012, A_sp{CP}{BR}( pi^+/-pi^mp) = { -}0.053+/-0.093+/-0.029, and A _sp{CP}{BR}(K3pi) - {-}0.018+/-0.023+/-0.002.. All measurements are consistent with most theoretical predictions and world average experimental values.

  20. Visual capture and the experience of having two bodies - Evidence from two different virtual reality techniques.

    PubMed

    Heydrich, Lukas; Dodds, Trevor J; Aspell, Jane E; Herbelin, Bruno; Bülthoff, Heinrich H; Mohler, Betty J; Blanke, Olaf

    2013-01-01

    In neurology and psychiatry the detailed study of illusory own body perceptions has suggested close links between bodily processing and self-consciousness. One such illusory own body perception is heautoscopy where patients have the sensation of being reduplicated and to exist at two or even more locations. In previous experiments, using a video head-mounted display, self-location and self-identification were manipulated by applying conflicting visuo-tactile information. Yet the experienced singularity of the self was not affected, i.e., participants did not experience having multiple bodies or selves. In two experiments presented in this paper, we investigated self-location and self-identification while participants saw two virtual bodies (video-generated in study 1 and 3D computer generated in study 2) that were stroked either synchronously or asynchronously with their own body. In both experiments, we report that self-identification with two virtual bodies was stronger during synchronous stroking. Furthermore, in the video generated setup with synchronous stroking participants reported a greater feeling of having multiple bodies than in the control conditions. In study 1, but not in study 2, we report that self-location - measured by anterior posterior drift - was significantly shifted towards the two bodies in the synchronous condition only. Self-identification with two bodies, the sensation of having multiple bodies, and the changes in self-location show that the experienced singularity of the self can be studied experimentally. We discuss our data with respect to ownership for supernumerary hands and heautoscopy. We finally compare the effects of the video and 3D computer generated head-mounted display technology and discuss the possible benefits of using either technology to induce changes in illusory self-identification with a virtual body.

  1. Site-directed mutations and kinetic studies show key residues involved in alkylammonium interactions and reveal two sites for phosphorylcholine in Pseudomonas aeruginosa phosphorylcholine phosphatase.

    PubMed

    Beassoni, Paola R; Otero, Lisandro H; Boetsch, Cristhian; Domenech, Carlos E; González-Nilo, Fernado D; Lisa, Angela T

    2011-07-01

    Pseudomonas aeruginosa phosphorylcholine phosphatase (PchP) catalyzes the hydrolysis of phosphorylcholine (Pcho) to produce choline and inorganic phosphate. PchP belongs to the haloacid dehalogenase superfamily (HAD) and possesses the three characteristic motifs of this family: motif I ((31)D and (33)D), motif II ((166)S), and motif III ((242)K, (261)G, (262)D and (267)D), which fold to form the catalytic site that binds the metal ion and the phosphate moiety of Pcho. Based on comparisons to the PHOSPHO1 and PHOSPHO2 human enzymes and the choline-binding proteins of Gram-(+) bacteria, we selected residues (42)E and (43)E and the aromatic triplet (82)YYY(84) for site-directed mutagenesis to study the interactions with Pcho and p-nitrophenylphosphate as substrates of PchP. Because mutations in (42)E, (43)E and the three tyrosine residues affect both the substrate affinity and the inhibitory effect produced by high Pcho concentrations, we postulate that two sites, one catalytic and one inhibitory, are present in PchP and that they are adjacent and share residues.

  2. Implications of two-body fragment decay for the interpretation of emission chronology from velocity-gated correlation functions

    SciTech Connect

    Helgesson, Johan; Ghetti, Roberta; Ekman, Joergen

    2006-04-15

    From velocity-gated small-angle correlation functions, the emission chronology can be deduced for nonidentical particles, if the emission is independent. This is not the case for nonidentical particles that originate from two-body decay of fragments. Experimental results may contain contributions from both independent emission and two-body decay, so care is needed in interpreting the velocity-gated correlation functions. It is shown that in some special cases, it is still possible to deduce the emission chronology, even if there is a contribution from two-body decay.

  3. Optimal definition of inter-residual contact in globular proteins based on pairwise interaction energy calculations, its robustness, and applications.

    PubMed

    Fačkovec, Boris; Vondrášek, Jiří

    2012-10-25

    Although a contact is an essential measurement for the topology as well as strength of non-covalent interactions in biomolecules and their complexes, there is no general agreement in the definition of this feature. Most of the definitions work with simple geometric criteria which do not fully reflect the energy content or ability of the biomolecular building blocks to arrange their environment. We offer a reasonable solution to this problem by distinguishing between "productive" and "non-productive" contacts based on their interaction energy strength and properties. We have proposed a method which converts the protein topology into a contact map that represents interactions with statistically significant high interaction energies. We do not prove that these contacts are exclusively stabilizing, but they represent a gateway to thermodynamically important rather than geometry-based contacts. The process is based on protein fragmentation and calculation of interaction energies using the OPLS force field and relies on pairwise additivity of amino acid interactions. Our approach integrates the treatment of different types of interactions, avoiding the problems resulting from different contributions to the overall stability and the different effect of the environment. The first applications on a set of homologous proteins have shown the usefulness of this classification for a sound estimate of protein stability.

  4. Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I.

    PubMed

    Kumar, Jitendra; Yadav, Viveka Nand; Phulera, Swastik; Kamble, Ashish; Gautam, Avneesh Kumar; Panwar, Hemendra Singh; Sahu, Arvind

    2017-10-01

    Poxviruses display species tropism-variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE (smallpox inhibitor of complement enzymes) exhibits selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP (vaccinia virus complement control protein) displays selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species specificity of VCP and SPICE for the classical pathway (CP). We observed that VCP is ∼43-fold superior to SPICE in inhibiting bovine CP. Further, functional assays revealed that increased inhibitory activity of VCP for bovine CP is solely due to its enhanced cofactor activity, with no effect on decay of bovine CP C3-convertase. To probe the structural basis of this specificity, we utilized single- and multi-amino-acid substitution mutants wherein 1 or more of the 11 variant VCP residues were substituted in the SPICE template. Examination of these mutants for their ability to inhibit bovine CP revealed that E108, E120, and E144 are primarily responsible for imparting the specificity and contribute to the enhanced cofactor activity of VCP. Binding and functional assays suggested that these residues interact with bovine factor I but not with bovine C4(H2O) (a moiety conformationally similar to C4b). Mapping of these residues onto the modeled structure of bovine C4b-VCP-bovine factor I supported the mutagenesis data. Taken together, our data help explain why the vaccine strain of vaccinia virus was able to gain a foothold in domesticated animals.IMPORTANCE Vaccinia virus was used for smallpox vaccination. The vaccine-derived virus is now circulating and causing outbreaks in dairy cattle in India and Brazil. However, the reason for this tropism is unknown. It is well recognized that the virus is susceptible to neutralization by the complement

  5. Trace analysis of dithiocarbamate fungicide residues on fruits and vegetables by hydrophilic interaction liquid chromatography/tandem mass spectrometry.

    PubMed

    Crnogorac, Goranka; Schmauder, Sabrina; Schwack, Wolfgang

    2008-08-01

    The simultaneous determination of dithiocarbamate (DTC) fungicide residues on fruits and vegetables was performed by liquid chromatography (LC) on a ZIC-pHILIC column coupled to tandem mass spectrometry (MS/MS). For each DTC subclass, i.e. dimethyldithiocarbamates (DMDs), ethylenebis(dithiocarbamates) (EBDs), and propylenebis(dithiocarbamates) (PBDs), the limits of detection and quantification were approximately 0.001 and 0.005 mg kg(-1), respectively. Recoveries from tomatoes, spiked in the range of 0.05-1 mg kg(-1), averaged between 97 and 101%. Several fruits and vegetables from a local market and different countries of origin (apples, pears, grapes, cherry tomatoes, cocktail tomatoes, cucumbers, tomatoes, tamarillos, papaya, and broccoli) were analyzed by LC/MS/MS, LC/MS, and by the routine CS(2) method. In general, the results obtained by both LC/MS and LC/MS/MS were in good agreement with those obtained by the CS(2) method except for the false positive CS(2) results for broccoli and papaya. The results demonstrate that both LC/MS and LC/MS/MS can be used for routine analyses of DTC residues, whereas LC/MS/MS is more sensitive and selective than LC/MS. Copyright (c) 2008 John Wiley & Sons, Ltd.

  6. Inorganic mercury interacts with cysteine residues (C451 and C474) of hOCT2 to reduce its transport activity.

    PubMed

    Pelis, Ryan M; Dangprapai, Yodying; Wunz, Theresa M; Wright, Stephen H

    2007-05-01

    Human organic cation transporter 2 (hOCT2) is essential for the renal tubular secretion of many toxic organic cations. Previously, of the cysteines (C437, C451, C470, and C474) that occur within transmembrane helices that comprise the hydrophilic cleft (proposed site of substrate binding), only C474 was accessible to maleimide-PEO(2)-biotin (hydrophilic thiol-reactive reagent), and covalent modification of this residue caused lower transport rates (Pelis RM, Zhang X, Dangprapai Y, Wright SH, J Biol Chem 281: 35272-35280, 2006). Thus it was hypothesized that the environmental contaminant Hg(2+) (as HgCl(2)) would interact with C474 to reduce hOCT2-mediated transport. Uptake of [(3)H]tetraethylammonium (TEA) into Chinese hamster ovary cells stably expressing hOCT2 was reduced in a concentration-dependent manner by HgCl(2), with an IC(50) of 3.9 +/- 0.11 microM. Treatment with 10 microM HgCl(2) caused a sixfold reduction in the maximal rate of TEA transport but did not alter the affinity of hOCT2 for TEA. To determine which cysteines interact with Hg(2+), a mutant with all four cleft cysteines converted to alanines (quadruple mutant), and four variants of this mutant, each with an individual cysteine restored, were created. The quadruple mutant was less sensitive to HgCl(2) than wild-type, whereas the C451- and C474-containing mutants were more sensitive than the quadruple mutant. Consistent with the HgCl(2) effect on transport, MTSEA-biotin only interacted with C451 and C474. These data indicate that C451 and C474 of hOCT2 reside in the aqueous milieu of the cleft and that interaction of Hg(2+) with these residues causes reduced TEA transport activity.

  7. β- transitions of 16 7N9 → 16 8O8 with optimized SDI residual interaction using pnTDA and TDA approximations

    NASA Astrophysics Data System (ADS)

    Pahlavani, M. R.; Firoozi, B.

    2015-11-01

    Within a developed particle-hole approach, a systematic study of the β- transition from the ground state of the 16N nucleus to the ground and some exited states of the 16O nucleus has been carried out. The energy spectrum and the wave functions of pure configuration of the 16N and 16O nuclei are numerically obtained using the mean-field shell model with respect to the Woods-Saxon nuclear potential accompanying spin-orbit and Coulomb interaction. Considering SDI residual interaction, mixed configuration of ground and excited pnTDA and TDA states are extracted for the aforementioned nucleus. These energy spectra and corresponding eigenstates are highly correspondent to the experimental energy spectrum and eigenstates after adjusting the residual potential parameters using the Nelder-Mead (NM) algorithm. In this approach, the endpoint energy, log ft and the partial half-lives of some possible transitions are calculated. The obtained results using the optimized SDI approach are reasonably close to the available experimental data.

  8. Arginine Residues on the Opposite Side of the Active Site Stimulate the Catalysis of Ribosome Depurination by Ricin A Chain by Interacting with the P-protein Stalk*

    PubMed Central

    Li, Xiao-Ping; Kahn, Peter C.; Kahn, Jennifer Nielsen; Grela, Przemysław; Tumer, Nilgun E.

    2013-01-01

    Ricin inhibits protein synthesis by depurinating the α-sarcin/ricin loop (SRL). Ricin holotoxin does not inhibit translation unless the disulfide bond between the A (RTA) and B (RTB) subunits is reduced. Ricin holotoxin did not bind ribosomes or depurinate them but could depurinate free RNA. When RTA is separated from RTB, arginine residues located at the interface are exposed to the solvent. Because this positively charged region, but not the active site, is blocked by RTB, we mutated arginine residues at or near the interface of RTB to determine if they are critical for ribosome binding. These variants were structurally similar to wild type RTA but could not bind ribosomes. Their Km values and catalytic rates (kcat) for an SRL mimic RNA were similar to those of wild type, indicating that their activity was not altered. However, they showed an up to 5-fold increase in Km and up to 38-fold decrease in kcat toward ribosomes. These results suggest that the stalk binding stimulates the catalysis of ribosome depurination by RTA. The mutated arginines have side chains behind the active site cleft, indicating that the ribosome binding surface of RTA is on the opposite side of the surface that interacts with the SRL. We propose that stalk binding stimulates the catalysis of ribosome depurination by orienting the active site of RTA toward the SRL and thereby allows docking of the target adenine into the active site. This model may apply to the translation factors that interact with the stalk. PMID:24003229

  9. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3′,5′difluorophenyl)-alanine

    PubMed Central

    Martín-Gago, Pablo; Rol, Álvaro; Todorovski, Toni; Aragón, Eric; Martin-Malpartida, Pau; Verdaguer, Xavier; Vallès Miret, Mariona; Fernández-Carneado, Jimena; Ponsati, Berta; Macias, Maria J.; Riera, Antoni

    2016-01-01

    Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1–5). We have designed six new Somatostatin analogs with L-3-(3′,5′-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID:27271737

  10. The interaction of partial public insurance programs and residual private insurance markets: evidence from the US Medicare program.

    PubMed

    Finkelstein, Amy

    2004-01-01

    A ubiquitous form of government intervention in insurance markets is to provide compulsory, but partial, public insurance coverage and to allow voluntary purchases of supplementary private insurance. This paper investigates the effects of such programs on insurance coverage for the risks not covered by the public program, using the example of the US Medicare program. I find that Medicare does not have substantial effects-in either direction-on coverage in residual private insurance markets. In particular, there is no evidence that Medicare is associated with reductions in private insurance coverage for prescription drug expenditures, an expenditure risk not covered by Medicare. Medicare is, however, associated with a shift in the source of prescription drug coverage, from employer-provided coverage to Medicare HMOs.

  11. Adsorption of charged protein residues on an inorganic nanosheet: Computer simulation of LDH interaction with ion channel

    NASA Astrophysics Data System (ADS)

    Tsukanov, Alexey A.; Psakhie, Sergey G.

    2016-08-01

    Quasi-two-dimensional and hybrid nanomaterials based on layered double hydroxides (LDH), cationic clays, layered oxyhydroxides and hydroxides of metals possess large specific surface area and strong electrostatic properties with permanent or pH-dependent electric charge. Such nanomaterials may impact cellular electrostatics, changing the ion balance, pH and membrane potential. Selective ion adsorption/exchange may alter the transmembrane electrochemical gradient, disrupting potential-dependent cellular processes. Cellular proteins as a rule have charged residues which can be effectively adsorbed on the surface of layered hydroxide based nanomaterials. The aim of this study is to attempt to shed some light on the possibility and mechanisms of protein "adhesion" an LDH nanosheet and to propose a new direction in anticancer medicine, based on physical impact and strong electrostatics. An unbiased molecular dynamics simulation was performed and the combined process free energy estimation (COPFEE) approach was used.

  12. Sperm surface hyaluronan binding protein (HABP1) interacts with zona pellucida of water buffalo (Bubalus bubalis) through its clustered mannose residues.

    PubMed

    Ghosh, Ilora; Datta, Kasturi

    2003-02-01

    Sperm-oocyte interaction during fertilization is multiphasic, with multicomponent events, taking place between zona pellucida (ZP) glycoproteins and sperm surface receptor. d-mannosylated glycoproteins, the major constituents of ZP are considered to serve as ligands for sperm binding. The presence of hyaluronan binding protein 1 (HABP1) on sperm surface of different mammals including cattle and its possible involvement in sperm function is already reported. Recently, we have demonstrated the specificity of clustered mannose as another ligand for HABP1 (Kumar et al., 2001: J Biosci 26:325-332). Here, we report that only N-linked mannosylated zona-glycoproteins bind to sperm surface HABP1. Labeled HABP1 interacts with ZP of intact oocyte of Bubalus bubalis, which can be competed with unlabeled HABP1 or excess d-mannosylated albumin (DMA). This data suggests the specific interaction of HABP1 with ZP, through clustered mannose residues. In order to examine the physiological significance of such an interaction, the capacity of sperm binding to oocytes under in vitro fertilization plates was examined either in presence of DMA alone or in combination with HABP1. The number of sperms, bound to oocytes was observed to reduce significantly in presence of DMA, which could be reversed by the addition of purified recombinant HABP1 (rHABP1) in the same plate. This suggests that sperm surface HABP1 may act as mannose binding sites for zona recognition. Copyright 2003 Wiley-Liss, Inc.

  13. Unique structure of Ascaris suum b5-type cytochrome: an additional α-helix and positively charged residues on the surface domain interact with redox partners

    PubMed Central

    Yokota, Takehiro; Nakajima, Yoshitaka; Yamakura, Fumiyuki; Sugio, Shigetoshi; Hashimoto, Muneaki; Takamiya, Shinzaburo

    2005-01-01

    Cytochrome b5 of the body wall of adult Ascaris suum, a porcine parasitic nematode, is a soluble protein that lacks a C-terminal membrane-anchoring domain, but possesses an N-terminal pre-sequence of 30 amino acids. During the maturation of cytochrome b5, the N-terminal pre-sequence is proteolytically cleaved to form the mature protein of 82 amino acid residues. A. suum cytochrome b5 is a basic protein containing more lysine residues and exhibiting a higher midpoint redox potential than its mammalian counterparts. We developed an expression system for the production of the recombinant nematode cytochrome b5, which is chemically and functionally identical with the native protein. Using this recombinant protein, we have determined the X-ray crystal structure of A. suum cytochrome b5 at 1.8 Å (1 Å=0.1 nm) resolution, and we have shown that this protein is involved in the reduction of nematode body-wall metmyoglobin. The crystal structure of A. suum cytochrome b5 consists of six α-helices and five β-strands. It differs from its mammalian counterparts by having a head-to-tail disulphide bridge, as well as a four-residue insertion in the vicinity of the sixth ligating histidine, which forms an additional α-helix, α4A, between helices α4 and α5. A. suum cytochrome b5 exists predominantly as a haem-orientation B isomer. Furthermore, the haem plane is rotated approx. 80° relative to the axis formed by haem-Fe and Nϵ atoms of the two histidine residues that are ligated to haem-Fe. The charge distribution around the haem crevice of A. suum cytochrome b5 is remarkably different from that of mammalian cytochrome b5 in that the nematode protein bears positively charged lysine residues surrounding the haem crevice. Using immunohistochemistry, we found that A. suum cytochrome b5 is present in the nematode hypodermis. Based on this histochemical and structural information, the physiological function of A. suum cytochrome b5 and its interaction with nematode

  14. Recognition of 5'-YpG-3' sequences by coupled stacking/hydrogen bonding interactions with amino acid residues.

    PubMed

    Lamoureux, Jason S; Maynes, Jason T; Glover, J N Mark

    2004-01-09

    The combined biochemical and structural study of hundreds of protein-DNA complexes has indicated that sequence-specific interactions are mediated by two mechanisms termed direct and indirect readout. Direct readout involves direct interactions between the protein and base-specific atoms exposed in the major and minor grooves of DNA. For indirect readout, the protein recognizes DNA by sensing conformational variations in the structure dependent on nucleotide sequence, typically through interactions with the phosphodiester backbone. Based on our recent structure of Ndt80 bound to DNA in conjunction with a search of the existing PDB database, we propose a new method of sequence-specific recognition that utilizes both direct and indirect readout. In this mode, a single amino acid side-chain recognizes two consecutive base-pairs. The 3'-base is recognized by canonical direct readout, while the 5'-base is recognized through a variation of indirect readout, whereby the conformational flexibility of the particular dinucleotide step, namely a 5'-pyrimidine-purine-3' step, facilitates its recognition by the amino acid via cation-pi interactions. In most cases, this mode of DNA recognition helps explain the sequence specificity of the protein for its target DNA.

  15. Spectral Deformation for Two-Body Dispersive Systems with e.g. the Yukawa Potential

    NASA Astrophysics Data System (ADS)

    Engelmann, Matthias; Rasmussen, Morten Grud

    2016-12-01

    We find an explicit closed formula for the k'th iterated commutator {{ad}Ak}(HV(ξ )) of arbitrary order k ⩾ 1 between a Hamiltonian HV(ξ )=M_{ω _{ξ }}+S_{\\check V} and a conjugate operator A={i}/2(v_{ξ}\\cdotnabla+nabla\\cdot v_{ξ}), where M_{ω _{ξ }} is the operator of multiplication with the real analytic function ω ξ which depends real analytically on the parameter ξ, and the operator S_{\\check V} is the operator of convolution with the (sufficiently nice) function \\check V, and v ξ is some vector field determined by ω ξ . Under certain assumptions, which are satisfied for the Yukawa potential, we then prove estimates of the form {{{ad}Ak}(HV(ξ ))(H0(ξ )+{i} )}|≤ C_{ξ }kk! where C ξ is some constant which depends continuously on ξ. The Hamiltonian is the fixed total momentum fiber Hamiltonian of an abstract two-body dispersive system and the work is inspired by a recent result [3] which, under conditions including estimates of the mentioned type, opens up for spectral deformation and analytic perturbation theory of embedded eigenvalues of finite multiplicity.

  16. Analytical Study of Periodic Solutions on Perturbed Equatorial Two-Body Problem

    NASA Astrophysics Data System (ADS)

    Abouelmagd, Elbaz I.; Mortari, Daniele; Selim, Hadia H.

    2015-12-01

    This paper presents analytical derivations to study periodic solutions for the two-body problem perturbed by the first zonal harmonic parameter. In particular, three different semianalytical approaches to solve this problem have been studied: (1) the classic perturbation theory, (2) the Lindstedt-Poincaré technique, and (3) the Krylov-Bogoliubov-Mitropolsky method. In addition, the numerical integration by Runge-Kutta algorithm is established. However, the numerical comparison tests show that by increasing the value of angular momentum the solutions provided by Lindstedt-Poincaré and Krylov-Bogoliubov-Mitropolsky methods become similar, and they provide almost identical results using a smaller value for the perturbed parameter which quantify the dynamical flattening of the main body, the Krylov-Bogoliubov-Mitropolsky provides more accurate results to design elliptical periodic solutions than Lindstedt-Poincaré technique when the perturbed parameter has a relatively large value, regardless of the value of angular momentum. This study can be applied to equatorial orbits to obtain closed-form analytical solutions.

  17. Modifying two-body relaxation in N-body systems by gas accretion

    NASA Astrophysics Data System (ADS)

    Leigh, Nathan; Sills, Alison; Böker, Torsten

    2013-08-01

    We consider the effects that accretion from the interstellar medium on to the particles of an N-body system has on the rate of two-body relaxation. To this end, we derive an accretion-modified relaxation time by adapting Spitzer's two-component model to include the damping effects of accretion. We consider several different mass- dependences and efficiency factors for the accretion rate, as well as different mass ratios for the two components of the model. The net effect of accretion is to accelerate mass segregation by increasing the average mass bar{m}, since the relaxation time is inversely proportional to bar{m}. Under the assumption that the accretion rate increases with the accretor mass, there are two additional effects that accelerate mass segregation. First, accretion acts to increase the range of any initial mass spectrum, quickly driving the heaviest members to even higher masses. Secondly, accretion acts to reduce the velocities of the accretors due to conservation of momentum, and it is the heaviest members that are affected the most. Using our two-component model, we quantify these effects as a function of the accretion rate, the total cluster mass and the component masses. We conclude by discussing the implications of our results for the dynamical evolution of primordial globular clusters, primarily in the context of black holes formed from the most massive stellar progenitors.

  18. Direct CP violation in two-body hadronic charmed meson decays

    NASA Astrophysics Data System (ADS)

    Cheng, Hai-Yang; Chiang, Cheng-Wei

    2012-02-01

    Motivated by the recent observation of CP violation in the charm sector by LHCb, we study direct CP asymmetries in the standard model (SM) for the singly Cabibbo-suppressed two-body hadronic decays of charmed mesons using the topological-diagram approach. In this approach, the magnitude and the phase of topological weak annihilation amplitudes, which arise mainly from final-state rescattering, can be extracted from the data. Consequently, direct CP asymmetry adir(tree) at tree level can be reliably estimated. In general, it lies in the range 10-4

  19. Medium modified two-body scattering amplitude from proton-nucleus total cross-sections

    NASA Technical Reports Server (NTRS)

    Tripathi, R. K.; Wilson, J. W.; Cucinotta, F. A.

    2001-01-01

    Recently (R.K. Tripathi, J.W. Wilson, F.A. Cucinotta, Nucl. Instr. and Meth. B 145 (1998) 277; R.K. Tripathi, F.A. Cucinotta, J.W. Wilson, NASA-TP-1998-208438), we have extracted nucleon-nucleon (N-N) cross-sections in the medium directly from experiment. The in-medium N-N cross-sections form the basic ingredients of several heavy-ion scattering approaches including the coupled-channel approach developed at the NASA Langley Research Center. Here, we investigate the ratio of real to imaginary part of the two-body scattering amplitude in the medium. These ratios are used in combination with the in-medium N-N cross-sections to calculate total proton-nucleus cross-sections. The agreement is excellent with the available experimental data. These cross-sections are needed for the radiation risk assessment of space missions. c2001 Elsevier Science B.V. All rights reserved.

  20. Two-body space dynamics technology demonstration for the BICEPS small satellite mission

    NASA Astrophysics Data System (ADS)

    Tyc, G.; Vigneron, F. R.; Jablonski, A. M.

    1993-11-01

    The recently proposed Canadian BICEPS mission requires co-orbiting two small satellites that allow for scientific experiments to be performed at a range of separation distances. Two implementation options have been identified; the preferred approach is to tether the two subsatellites and spin them to maintain tension in the tether. The other is to use two free-flying small satellites with reaction control capability on one satellite so that it can be maneuvered relative to the other. One of the scientific objectives of BICEPS is to study the dynamics of this two-body configuration. The proposed dynamics related research activities associated with the tethered satellite configuration are described along with its deployment strategy and a preliminary dynamics analysis. It is shown that a cold-gas propulsion system is needed on at least one subsatellite to spin up the system at several stages during tether deployment in order to maintain tether tensions below 2,250 N. A brief research summary is also provided for the free-flying configuration.

  1. Two-body space dynamics technology demonstration for the biceps small satellite mission

    NASA Astrophysics Data System (ADS)

    Tyc, G.; Vigneron, F. R.; Jablonski, A. M.

    1994-03-01

    The recently proposed Canadian BICEPS mission requires co-orbiting two small satellites that allow for scientific experiments to be performed at a range of separation distances. Two implementation options have been identified: the preferred approach is to tether the two subsatellites and spin them in a cartwheeling manner to maintain tension in the tether; and the other is to use two free-flying small satellites with reaction control capability on one satellite so that it can be maneuvered relative to the other. One of the scientific objectives of the BICEPS mission is to study the dynamics of this two-body configuration. This paper primarily describes the proposed dynamics-related research activities associated with the tethered configuration, and a brief research summary is provided for the free-flying configuration. The deployment strategy of the tethered configuration is also described and a preliminary dynamics analysis is presented. It is shown that a cold-gas propulsion system is needed on at least one subsatellite to spin-up the system at several stages during the tether deployment in order to maintain tether tensions below 2250 N (approximately 500 lb). Generally, it is believed that the BICEPS mission offers possibilities for technology advancement of co-orbiting small satellites, and in particular tethered small satellites - and in so doing would develop a Canadian niche technology area.

  2. Analysis of charmless two-body B decays in factorization-assisted topological-amplitude approach

    NASA Astrophysics Data System (ADS)

    Zhou, Si-Hong; Zhang, Qi-An; Lyu, Wei-Ran; Lü, Cai-Dian

    2017-02-01

    We analyze charmless two-body non-leptonic B decays B → PP, PV under the framework of a factorization-assisted topological-amplitude approach, where P( V) denotes a light pseudoscalar (vector) meson. Compared with the conventional flavor diagram approach, we consider the flavor SU(3) breaking effect assisted by a factorization hypothesis for topological diagram amplitudes of different decay modes, factorizing out the corresponding decay constants and form factors. The non-perturbative parameters of topology diagram magnitudes χ and the strong phase φ are universal; they can be extracted by χ ^2 fit from current abundant experimental data of charmless Bdecays. The number of free parameters and the χ ^2 per degree of freedom are both reduced compared with previous analyses. With these best fitted parameters, we predict branching fractions and CP asymmetry parameters of nearly 100 B_{u,d} and B_s decay modes. The long-standing π π and π K- CP puzzles are solved simultaneously.

  3. Two-Body Photodisintegration of ^4He into p+t

    NASA Astrophysics Data System (ADS)

    Nasseripour, Rakhsha; Berman, Barry

    2008-10-01

    The two-body photodisintegration of ^4He into a proton and a triton has been studied using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid ^4He target. This is the first measurement of the photodisintegration of ^4He above 0.4 GeV. The differential cross sections for the γ^4He-> pt reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by Laget [1]. At 0.6-0.8 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. At the same time, the strength of the one-body mechanisms is overestimated at higher energies and at small proton-scattering angles. These results reinforce the conclusion of our previous study of the three-body breakup of ^3He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV [2]. [1] J.-M. Laget, private communication (2008) [2] S. Niccolai et al., Phys. Rev. C 70, 064003 (2004)

  4. The factor VIIIa C2 domain (residues 2228-2240) interacts with the factor IXa Gla domain in the factor Xase complex.

    PubMed

    Soeda, Tetsuhiro; Nogami, Keiji; Nishiya, Katsumi; Takeyama, Masahiro; Ogiwara, Kenichi; Sakata, Yoichi; Yoshioka, Akira; Shima, Midori

    2009-02-06

    Factor VIIIa functions as a cofactor for factor IXa in the phospholipid surface-dependent activation of factor X. Both the C2 domain of factor VIIIa and the Gla domain of factor IXa are involved in phospholipid binding and are required for the activation of factor X. In this study, we have examined the close relationship between these domains in the factor Xase complex. Enzyme-linked immunosorbent assay-based and surface plasmon resonance-based assays in the absence of phospholipid showed that Glu-Gly-Arg active site-modified factor IXa bound to immobilized recombinant C2 domain (rC2) dose-dependently (Kd = 108 nm). This binding ability was optimal under physiological conditions. A monoclonal antibody against the Gla domain of factor IXa inhibited binding by approximately 95%, and Gla domainless factor IXa failed to bind to rC2. The addition of monoclonal antibody or rC2 with factor VIIIa inhibited factor IXa-catalyzed factor X activation in the absence of phospholipid. Inhibition was not evident, however, in similar experiments in the absence of factor VIIIa, indicating that the C2 domain interacted with the Gla domain of factor IXa. A fragment designated C2-(2182-2259), derived from V8 protease-cleaved rC2, bound to Glu-Gly-Arg active site-modified factor IXa. Competitive assays, using overlapping synthetic peptides encompassing residues 2182-2259, demonstrated that peptide 2228-2240 significantly inhibited both this binding and factor Xa generation, independently of phospholipid. Our results indicated that residues 2228-2240 in the factor VIIIa C2 domain constitutes an interactive site for the Gla domain of factor IXa. The findings provide the first evidence for an essential role for this interaction in factor Xase assembly.

  5. A PM7 dynamic residue-ligand interactions energy landscape of the BACE1 inhibitory pathway by hydroxyethylamine compounds. Part I: The flap closure process.

    PubMed

    Gueto-Tettay, Carlos; Martinez-Consuegra, Alejandro; Zuchniarz, Joshua; Gueto-Tettay, Luis Roberto; Drosos-Ramírez, Juan Carlos

    2017-09-01

    BACE1 is an enzyme of scientific interest because it participates in the progression of Alzheimer's disease. Hydroxyethylamines (HEAs) are a family of compounds which exhibit inhibitory activity toward BACE1 at a nanomolar level, favorable pharmacokinetic properties and oral bioavailability. The first step in the inhibition of BACE1 by HEAs consists of their entrance into the protease active site and the resultant conformational change in the protein, from Apo to closed form. These two conformations differ in the position of an antiparallel loop (called the flap) which covers the entrance to the catalytic site. For BACE1, closure of this flap is vital to its catalytic activity and to inhibition of the enzyme due to the new interactions thereby formed with the ligand. In the present study a dynamic energy landscape of residue-ligand interaction energies (ReLIE) measured for 112 amino acids in the BACE1 active site and its immediate vicinity during the closure of the flap induced by 8 HEAs of different inhibitory power is presented. A total of 6.272 million ReLIE calculations, based on the PM7 semiempirical method, provided a deep and quantitative view of the first step in the inhibition of the aspartyl protease. The information suggests that residues Asp93, Asp289, Thr292, Thr293, Asn294 and Arg296 are anchor points for the ligand, accounting for approximately 45% of the total protein-ligand interaction. Additionally, flap closure improved the BACE1-HEA interaction by around 25%. Furthermore, the inhibitory activity of HEAs could be related to the capacity of these ligands to form said anchor point interactions and maintain them over time: the lack of some of these anchor interactions delayed flap closure or impeded it completely, or even caused the flap to reopen. The methodology employed here could be used as a tool to evaluate future structural modifications which lead to improvements in the favorability and stability of BACE1-HEA ReLIEs, aiding in the design of

  6. The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication*

    PubMed Central

    Tay, Moon Y. F.; Saw, Wuan Geok; Zhao, Yongqian; Chan, Kitti W. K.; Singh, Daljit; Chong, Yuwen; Forwood, Jade K.; Ooi, Eng Eong; Grüber, Gerhard; Lescar, Julien; Luo, Dahai; Vasudevan, Subhash G.

    2015-01-01

    Dengue virus multifunctional proteins NS3 protease/helicase and NS5 methyltransferase/RNA-dependent RNA polymerase form part of the viral replication complex and are involved in viral RNA genome synthesis, methylation of the 5′-cap of viral genome, and polyprotein processing among other activities. Previous studies have shown that NS5 residue Lys-330 is required for interaction between NS3 and NS5. Here, we show by competitive NS3-NS5 interaction ELISA that the NS3 peptide spanning residues 566–585 disrupts NS3-NS5 interaction but not the null-peptide bearing the N570A mutation. Small angle x-ray scattering study on NS3(172–618) helicase and covalently linked NS3(172–618)-NS5(320–341) reveals a rigid and compact formation of the latter, indicating that peptide NS5(320–341) engages in specific and discrete interaction with NS3. Significantly, NS3:Asn-570 to alanine mutation introduced into an infectious DENV2 cDNA clone did not yield detectable virus by plaque assay even though intracellular double-stranded RNA was detected by immunofluorescence. Detection of increased negative-strand RNA synthesis by real time RT-PCR for the NS3:N570A mutant suggests that NS3-NS5 interaction plays an important role in the balanced synthesis of positive- and negative-strand RNA for robust viral replication. Dengue virus infection has become a global concern, and the lack of safe vaccines or antiviral treatments urgently needs to be addressed. NS3 and NS5 are highly conserved among the four serotypes, and the protein sequence around the pinpointed amino acids from the NS3 and NS5 regions are also conserved. The identification of the functionally essential interaction between the two proteins by biochemical and reverse genetics methods paves the way for rational drug design efforts to inhibit viral RNA synthesis. PMID:25488659

  7. Spring Chinook Salmon Interactions Indices and Residual/Precocial Monitoring in the Upper Yakima Basin; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2001-2002 Annual Report.

    SciTech Connect

    Pearsons, Todd N.; James, Brenda B.; Johnson, Christopher L.

    2003-05-01

    This report examines some of the factors that can influence the success of supplementation, which is currently being tested in the Yakima Basin using upper Yakima stock of spring chinook salmon. Supplementation success in the Yakima Basin is defined relative to four topic areas: natural production, genetics, ecological interactions, and harvest (Busack et al. 1997). The success of spring chinook salmon supplementation in the Yakima Basin is dependent, in part, upon fish culture practices and favorable physical and biological conditions in the natural environment (Busack et al. 1997). Shortfalls in either of these two topics (i.e., failure in culturing many fish that have high long-term fitness or environmental conditions that constrain spring chinook salmon production) will cause supplementation success to be limited. For example, inadvertent selection or propagation of spring chinook that residualize or precocially mature may hinder supplementation success. Spring chinook salmon that residualize (do not migrate during the normal migration period) may have lower survival rates than migrants and, additionally, may interact with wild fish and cause unacceptable impacts to non-target taxa. Large numbers of precocials (nonanadromous spawners) may increase competition for females and significantly skew ratios of offspring sired by nonanadromous males, which could result in more nonanadromous spring chinook in future generations. Conditions in the natural environment may also limit the success of spring chinook supplementation. For example, intra or interspecific competition may constrain spring chinook salmon production. Spring chinook salmon juveniles may compete with each other for food or space or compete with other species that have similar ecological requirements. Monitoring of spring chinook salmon residuals, precocials, prey abundance, carrying capacity, and competition will help researchers interpret why supplementation is working or not working (Busack et al

  8. Elicitin-membrane interaction is driven by a positive charge on the protein surface: role of Lys13 residue in lipids loading and resistance induction.

    PubMed

    Plešková, Veronika; Kašparovský, Tomáš; Obořil, Michal; Ptáčková, Nikola; Chaloupková, Radka; Ladislav, Dokládal; Damborský, Jiří; Lochman, Jan

    2011-03-01

    Elicitins are family of small proteins secreted by species of the pathogenic fungus Phytophthora inducing a defence reaction in plants. They contain a hydrophobic cavity capable of binding sterols and fatty acids, and on the basis of their pI they are classified as either α-elicitins or more necrotising β-elicitins. The residue Lys13 was previously identified as a key determinant of the necrotising activity of basic elicitins. In the present study we describe changes in the ability of cryptogein, a β-elicitin inducing a hypersensitive response in tobacco, to transfer sterols and fatty acids between micelles and liposomes upon Lys13Val mutation. We propose that the change in activity is influenced by the elimination of positive charge on the surface of cryptogein, which is significant for correct positioning of the protein during lipid loading, without adversely affecting the binding of sterol to the cavity of the protein. Compared to wild type cryptogein, mutation Lys13Val resulted in lowered expression of defence-related genes and compromised resistance to Phytophthora parasitica. Furthermore, resistance induced by Lys13Val mutant was similar to that induced by acidic elicitin capsicein containing at amino position 13 valine Determined results sustained a crucial role of positive lysine residues on the surface of basic elicitins and suggested their significant role in correct protein-membrane interaction and thus on their biological activity.

  9. Nonleptonic two-body B decays including axial-vector mesons in the final state

    SciTech Connect

    Calderon, G.; Munoz, J. H.; Vera, C. E.

    2007-11-01

    We present a systematic study of exclusive charmless nonleptonic two-body B decays including axial-vector mesons in the final state. We calculate branching ratios of B{yields}PA, VA, and AA decays, where A, V, and P denote an axial vector, a vector, and a pseudoscalar meson, respectively. We assume a naive factorization hypothesis and use the improved version of the nonrelativistic Isgur-Scora-Grinstein-Wise quark model for form factors in B{yields}A transitions. We include contributions that arise from the effective {delta}B=1 weak Hamiltonian H{sub eff}. The respective factorized amplitudes of these decays are explicitly shown and their penguin contributions are classified. We find that decays B{sup -}{yields}a{sub 1}{sup 0}{pi}{sup -}, B{sup 0}{yields}a{sub 1}{sup {+-}}{pi}{sup {+-}}, B{sup -}{yields}a{sub 1}{sup -}K{sup 0}, B{sup 0}{yields}a{sub 1}{sup +}K{sup -}, B{sup 0}{yields}f{sub 1}K{sup 0}, B{sup -}{yields}f{sub 1}K{sup -}, B{sup -}{yields}K{sub 1}{sup -}(1400){eta}{sup (')}, B{sup -}{yields}b{sub 1}{sup -}K{sup 0}, and B{sup 0}{yields}b{sub 1}{sup +}{pi}{sup -}(K{sup -}) have branching ratios of the order of 10{sup -5}. We also study the dependence of branching ratios for B{yields}K{sub 1}P(V,A) decays [K{sub 1}=K{sub 1}(1270), K{sub 1}(1400)] with respect to the mixing angle between K{sub 1A} and K{sub 1B}.

  10. Nonlocality in many-body quantum systems detected with two-body correlators

    SciTech Connect

    Tura, J.; Augusiak, R.; Sainz, A.B.; Lücke, B.; Klempt, C.; Lewenstein, M.; Acín, A.

    2015-11-15

    Contemporary understanding of correlations in quantum many-body systems and in quantum phase transitions is based to a large extent on the recent intensive studies of entanglement in many-body systems. In contrast, much less is known about the role of quantum nonlocality in these systems, mostly because the available multipartite Bell inequalities involve high-order correlations among many particles, which are hard to access theoretically, and even harder experimentally. Standard, “theorist- and experimentalist-friendly” many-body observables involve correlations among only few (one, two, rarely three...) particles. Typically, there is no multipartite Bell inequality for this scenario based on such low-order correlations. Recently, however, we have succeeded in constructing multipartite Bell inequalities that involve two- and one-body correlations only, and showed how they revealed the nonlocality in many-body systems relevant for nuclear and atomic physics [Tura et al., Science 344 (2014) 1256]. With the present contribution we continue our work on this problem. On the one hand, we present a detailed derivation of the above Bell inequalities, pertaining to permutation symmetry among the involved parties. On the other hand, we present a couple of new results concerning such Bell inequalities. First, we characterize their tightness. We then discuss maximal quantum violations of these inequalities in the general case, and their scaling with the number of parties. Moreover, we provide new classes of two-body Bell inequalities which reveal nonlocality of the Dicke states—ground states of physically relevant and experimentally realizable Hamiltonians. Finally, we shortly discuss various scenarios for nonlocality detection in mesoscopic systems of trapped ions or atoms, and by atoms trapped in the vicinity of designed nanostructures.

  11. Potential of lignin from Canna edulis ker residue in the inhibition of α-d-glucosidase: Kinetics and interaction mechanism merging with docking simulation.

    PubMed

    Xie, Fan; Gong, Shengxiang; Zhang, Wei; Wu, Jinhong; Wang, Zhengwu

    2017-02-01

    In this study, we extracted lignin from Canna edulis ker residue. Its chemical structure, inhibitory activity on α-d-glucosidase, and kinetics as well as interaction mechanism were investigated by using spectrum analysis and docking simulation. The isolated lignin was composed by guaiacyl and syringal units, and exhibited stronger inhibition on α-d-glucosidase than acarbose with the half maximal inhibitory concentration at 5.3±0.3μM. It was a non-competitive inhibitior with Km and Ki values of 0.53±0.02mM and 0.92±0.12μM, respectively. It could quench the intrinsic fluorescence of α-d-glucosidase through a static quenching mode. The calculated values of enthalpy and entropy change were 20.8±2.5kJmol(-1) and 172.7±0.8Jmol(-1)K(-1), respectively. There was a single binding site on α-d-glucosidase for lignin, and the binding distance was 3.2nm. The molecular docking analysis exhibited that the hydrogen bonds, hydropholic interaction, and van der Waals forces were the main forces for lignin bind to α-d-glucosidase. This work provides a new insight into the interaction between the lignin and α-d-glucosidase, which might be beneficial to type 2 diabetes with the application of lignin in functional food and pharmacy fields.

  12. Involvement of the catalytically important Asp54 residue of Mycobacterium smegmatis DevR in protein-protein interactions between DevR and DevS.

    PubMed

    Lee, Ha-Na; Lee, Na-On; Ko, In-Jeong; Kim, Si Wouk; Kang, Beom Sik; Oh, Jeong-Il

    2013-06-01

    The DevSR two-component system in Mycobacterium smegmatis consists of the DevS histidine kinase and the DevR response regulator. It is a regulatory system that is involved in the adaptation of mycobacteria to hypoxic and NO stresses. Using the yeast two-hybrid assay and pull-down assay, it was demonstrated that the phosphoaccepting Asp (Asp54) of DevR is important for protein-protein interactions between DevR and DevS. The negative charge of Asp54 of DevR was shown to play an important role in protein-protein interactions between DevR and DevS. When the Lys104 residue, which is involved in transmission of conformational changes induced by phosphorylation of the response regulator, was replaced with Ala, the mutant form of DevR was not phosphorylated by DevS and functionally inactive in vivo. However, the K104A mutation in DevR only slightly affected protein-protein interactions between DevR and DevS. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. Regions and residues of an asymmetric operator DNA interacting with the monomeric repressor of temperate mycobacteriophage L1.

    PubMed

    Bandhu, Amitava; Ganguly, Tridib; Jana, Biswanath; Mondal, Rajkrishna; Sau, Subrata

    2010-05-18

    Previously, the repressor protein of mycobacteriophage L1 bound to two operator DNAs with dissimilar affinity. Surprisingly, the putative operator consensus sequence, 5'GGTGGa/cTGTCAAG, lacks the dyad symmetry reported for the repressor binding operators of lambda and related phages. To gain insight into the structure of the L1 repressor-asymmetric operator DNA complex, we have performed various in vitro experiments. A dimethyl sulfate protection assay revealed that five guanine bases, mostly distributed in the two adjacent major grooves of the 13 bp operator DNA helix, participate in repressor binding. Hydroxyl radical footprinting demonstrated that interaction between the repressor and operator DNA is asymmetric in nature and occurs primarily through one face of the DNA helix. Genetic studies not only confirmed the results of the dimethyl sulfate protection assay but also indicated that other bases in the 13 bp operator DNA are critical for repressor binding. Interestingly, repressor that weakly induced bending in the asymmetric operator DNA interacted with this operator as a monomer. The tertiary structure of the L1 repressor-operator DNA complex therefore appears to be distinct from those of the lambdoid phages even though the number of repressor molecules per operator site closely matched that of the lambda phage system.

  14. INTERACTIONS OF DIFFERENT INHIBITORS WITH ACTIVE-SITE ASPARTYL RESIDUES OF HIV-1 PROTEASE AND POSSIBLE RELEVANCE TO PEPSINS

    PubMed Central

    Sayer, Jane M.; Louis, John M.

    2008-01-01

    The importance of the active site region aspartyl residues 25 and 29 of the mature HIV-1 protease (PR) for the binding of five clinical and three experimental protease inhibitors (symmetric cyclic urea inhibitor DMP323, non-hydrolysable substrate analog (RPB) and the generic aspartic protease inhibitor acetyl-pepstatin (Ac-PEP)) was assessed by differential scanning calorimetry. ΔTm values, defined as the difference in Tm for a given protein in the presence and absence of inhibitor, for PR with DRV, ATV, SQV, RTV, APV, DMP323, RPB and Ac-PEP are 22.4, 20.8, 19.3, 15.6, 14.3, 14.7, 8.7, and 6.5 °C, respectively. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by ΔTm ratios [ΔTm(PR)/ΔTm(PRD25N)] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (ΔTm ratios of 1-2) is least affected. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (ΔTm(PR)/ΔTm(PRD29N) ≥ 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (ΔTm ratios of 1.4-2.2). Of the 9 FDA approved clinical HIV-1 protease inhibitors screened, APV, RTV and DRV competitively inhibit porcine pepsin with Ki values of 0.3, 0.6 and 2.14 μM, respectively. DSC results were consistent with this relatively weak binding of APV (ΔTm 2.7 °C) compared with the tight binding of AcPEP (ΔTm ≥17 °C). Comparison of superimposed structures of the PR/APV complex with those of PR/Ac-PEP and pepsin/pepstatin A complexes suggests a role for Asp215, Asp32 and Ser219 in pepsin, equivalent to Asp25, Asp25′ and Asp29 in PR, in the binding and stabilization of the pepsin/APV complex. PMID:18951411

  15. Interactions of different inhibitors with active-site aspartyl residues of HIV-1 protease and possible relevance to pepsin.

    PubMed

    Sayer, Jane M; Louis, John M

    2009-05-15

    The importance of the active site region aspartyl residues 25 and 29 of the mature HIV-1 protease (PR) for the binding of five clinical and three experimental protease inhibitors [symmetric cyclic urea inhibitor DMP323, nonhydrolyzable substrate analog (RPB) and the generic aspartic protease inhibitor acetyl-pepstatin (Ac-PEP)] was assessed by differential scanning calorimetry. DeltaT(m) values, defined as the difference in T(m) for a given protein in the presence and absence of inhibitor, for PR with DRV, ATV, SQV, RTV, APV, DMP323, RPB, and Ac-PEP are 22.4, 20.8, 19.3, 15.6, 14.3, 14.7, 8.7, and 6.5 degrees C, respectively. Binding of APV and Ac-PEP is most sensitive to the D25N mutation, as shown by DeltaT(m) ratios [DeltaT(m)(PR)/DeltaT(m)(PR(D25N))] of 35.8 and 16.3, respectively, whereas binding of DMP323 and RPB (DeltaT(m) ratios of 1-2) is least affected. Binding of the substrate-like inhibitors RPB and Ac-PEP is nearly abolished (DeltaT(m)(PR)/DeltaT(m)(PR(D29N)) > or = 44) by the D29N mutation, whereas this mutation only moderately affects binding of the smaller inhibitors (DeltaT(m) ratios of 1.4-2.2). Of the nine FDA-approved clinical HIV-1 protease inhibitors screened, APV, RTV, and DRV competitively inhibit porcine pepsin with K(i) values of 0.3, 0.6, and 2.14 microM, respectively. DSC results were consistent with this relatively weak binding of APV (DeltaT(m) 2.7 degrees C) compared with the tight binding of Ac-PEP (DeltaT(m) > or = 17 degrees C). Comparison of superimposed structures of the PR/APV complex with those of PR/Ac-PEP and pepsin/pepstatin A complexes suggests a role for Asp215, Asp32, and Ser219 in pepsin, equivalent to Asp25, Asp25', and Asp29 in PR in the binding and stabilization of the pepsin/APV complex.

  16. Interaction of biochar and organic residues from sugarcane industry in soil chemical attributes and greenhouse gases emissions.

    NASA Astrophysics Data System (ADS)

    Fernanda Abbruzzini, Thalita; Feola Conz, Rafaela; Pellegrino Cerri, Carlos Eduardo

    2014-05-01

    Researchers have highlighted the importance of providing soil quality in agricultural systems, besides mitigating greenhouse gases (GHG) emissions to the atmosphere and increasing soil carbon sequestration. Therefore, several studies have demonstrated the effectiveness of biochar as a soil conditioner, both in relation to increased C sequestration and improvements in soil chemical, physical and biological attributes, resulting in better conditions for plant growth. The aim of this study was to assess the impact of applying biochar produced from sugarcane straw to soils in relation to changes in soil chemical attributes and mitigation of greenhouse gases emissions into the atmosphere. To do so, we conducted a laboratory incubation under controlled environmental conditions (ie temperature and humidity) with and without the application of filter cake and vinasse (ie organic residues from sugarcane industry) and rates of biochar application (0, 10, 20 and 50 Mg ha-1). The fluxes of CO2, N2O and CH4 of each incubation unity were measured periodically (in days 1, 2, 5, 9, 13, 16, 20, 24, 28, 30, 47, 60, 91, 105, 123, 130, 138 and 150). Each treatment consisted of eight replicates with destructive samples evaluated at 30, 60, 90 and 150 days after incubation to characterize the chemical attributes of the incubated soil, besides GHG (CO2, N2O and CH4) emissions. In general, there was an increase in carbon dioxide (CO2) fluxes over time due to the application of filter cake and vinasse and increasing dose of biochar. Regarding nitrous oxide (N2O) emissions, there was an increase of 82.35% with the application of vinasse and filter cake compared to the control treatment. However, different doses of biochar (10, 20 and 50 Mg ha-1) reduced N2O emissions by 29, 38.7 and 70.9%, respectively. The methane (CH4) flux was negligible in all treatments. We observed improvements in soil chemical attributes, such as higher pH, a substantial increase in the soil CEC, reduced exchangeable

  17. Arginine residues on the opposite side of the active site stimulate the catalysis of ribosome depurination by ricin A chain by interacting with the P-protein stalk.

    PubMed

    Li, Xiao-Ping; Kahn, Peter C; Kahn, Jennifer Nielsen; Grela, Przemyslaw; Tumer, Nilgun E

    2013-10-18

    Ricin inhibits protein synthesis by depurinating the α-sarcin/ricin loop (SRL). Ricin holotoxin does not inhibit translation unless the disulfide bond between the A (RTA) and B (RTB) subunits is reduced. Ricin holotoxin did not bind ribosomes or depurinate them but could depurinate free RNA. When RTA is separated from RTB, arginine residues located at the interface are exposed to the solvent. Because this positively charged region, but not the active site, is blocked by RTB, we mutated arginine residues at or near the interface of RTB to determine if they are critical for ribosome binding. These variants were structurally similar to wild type RTA but could not bind ribosomes. Their K(m) values and catalytic rates (k(cat)) for an SRL mimic RNA were similar to those of wild type, indicating that their activity was not altered. However, they showed an up to 5-fold increase in K(m) and up to 38-fold decrease in kcat toward ribosomes. These results suggest that the stalk binding stimulates the catalysis of ribosome depurination by RTA. The mutated arginines have side chains behind the active site cleft, indicating that the ribosome binding surface of RTA is on the opposite side of the surface that interacts with the SRL. We propose that stalk binding stimulates the catalysis of ribosome depurination by orienting the active site of RTA toward the SRL and thereby allows docking of the target adenine into the active site. This model may apply to the translation factors that interact with the stalk.

  18. Interaction of acid mine drainage with Ordinary Portland Cement blended solid residues generated from active treatment of acid mine drainage with coal fly ash.

    PubMed

    Gitari, Wilson M; Petrik, Leslie F; Key, David L; Okujeni, Charles

    2011-01-01

    Fly ash (FA) has been investigated as a possible treatment agent for Acid mine drainage (AMD) and established to be an alternative, cheap and economically viable agent compared to the conventional alkaline agents. However, this treatment option also leads to generation of solid residues (SR) that require disposal and one of the proposed disposal method is a backfill in coal mine voids. In this study, the interaction of the SR with AMD that is likely to be present in such backfill scenario was simulated by draining columns packed with SR and SR + 6% Ordinary Portland Cement (OPC) unsaturated with simulated AMD over a 6 month period. The evolving geochemistry of the liquid/solid (L/S) system was evaluated in-terms of the mineral phases likely or controlling contaminants attenuation at the different pH regimes generated. Stepwise acidification of the percolates was observed as the drainage progressed. Two pH buffer zones were observed (7.5-9 and 3-4) for SR and (11.2-11.3 and 3.5-4) for SR + 6% OPC. The solid residue cores (SR) appeared to have a significant buffering capacity, maintaining a neutral to slightly alkaline pH in the leachates for an extended period of time (97 days: L/S 4.3) while SR + 6% OPC reduced this neutralization capacity to 22 days (L/S 1.9). Interaction of AMD with SR or SR + 6% OPC generated alkaline conditions that favored precipitation of Fe, Al, Mn-(oxy) hydroxides, Fe and Ca-Al hydroxysulphates that greatly contributed to the contaminants removal. However, precipitation of these phases was restricted to the pH of the leachates remaining at neutral to circum-neutral levels. Backfill of mine voids with SR promises to be a feasible technology for the disposal of the SR but its success will greatly depend on the disposal scenario, AMD generated and the alkalinity generating potential of the SR. A disadvantage would be the possible re-dissolution of the precipitated phases at pH < 4 that would release the contaminants back to the water column

  19. Rates and C P asymmetries of charmless two-body baryonic Bu ,d ,s decays

    NASA Astrophysics Data System (ADS)

    Chua, Chun-Khiang

    2017-05-01

    With the experimental evidences of B¯ 0→p p ¯ and B-→Λ p ¯ decays, it is now possible to extract both tree and penguin amplitudes of the charmless two-body baryonic B decays for the first time. The extracted penguin-tree ratio agrees with the expectation. Using the topological amplitude approach with the experimental results on B¯ 0→p p ¯ and B-→Λ p ¯ decay rates as input, predictions on all other B¯ q→B B ¯ , B D ¯ , D B ¯ and D D ¯ decay rates, where B and D are the low lying octet and decuplet baryons, respectively, are given. It is nontrivial that the results do not violate any existing experimental upper limit. From the analysis it is understandable that why B¯ 0→p p ¯ and B-→Λ p ¯ modes are the first two modes with experimental evidences. Relations on rates are verified using the numerical results. We note that the predicted B-→p Δ++ ¯ rate is close to the experimental bound, which has not been updated in the last ten years. Direct C P asymmetries of all B¯q→B B ¯, B D ¯, D B ¯ and D D ¯ modes are explored. Relations on C P asymmetries are examined using the numerical results. The direct C P asymmetry of B¯ 0→p p ¯ decay can be as large as ±50 %. Some of the C P asymmetries can serve as tests of the Standard Model. Most of them are pure penguin modes, which are expected to be sensitive to new physics contributions. In particular, B¯s 0→Ξ-Ξ- ¯ , B¯ 0→Ξ-Σ*- ¯ , B¯ 0→Ω-Ξ- ¯ , B¯s 0→Σ*-Σ*- ¯ , B¯s 0→Ω-Ω- ¯ , B¯s 0→Ξ-Ξ*- ¯ , B¯s 0→Ξ*-Ξ- ¯ , B¯ 0→Ξ*-Σ*- ¯ , B¯ 0→Ω-Ξ*- ¯ and B¯s 0→Ξ*-Ξ*- ¯ decays are Δ S =-1 pure penguin modes with unsuppressed rates, which can be searched in the near future. Their C P asymmetries are constrained to be of few % and are good candidates to be added to the list of the tests of the Standard Model.

  20. The residue at position 5 of the N-terminal region of Src and Fyn modulates their myristoylation, palmitoylation, and membrane interactions

    PubMed Central

    Gottlieb-Abraham, Efrat; Gutman, Orit; Pai, Govind M.; Rubio, Ignacio; Henis, Yoav I.

    2016-01-01

    The interactions of Src family kinases (SFKs) with the plasma membrane are crucial for their activity. They depend on their fatty-acylated N-termini, containing N-myristate and either a polybasic cluster (in Src) or palmitoylation sites (e.g., Fyn). To investigate the roles of these moieties in SFK membrane association, we used fluorescence recovery after photobleaching beam-size analysis to study the membrane interactions of c-Src-GFP (green fluorescent protein) or Fyn-GFP fatty-acylation mutants. Our studies showed for the first time that the membrane association of Fyn is more stable than that of Src, an effect lost in a Fyn mutant lacking the palmitoylation sites. Unexpectedly, Src-S3C/S6C (containing cysteines at positions 3/6, which are palmitoylated in Fyn) exhibited fast cytoplasmic diffusion insensitive to palmitoylation inhibitors, suggesting defective fatty acylation. Further replacement of the charged Lys-5 by neutral Gln to resemble Fyn (Src-S3C/S6C/K5Q) restored Fyn-like membrane interactions, indicating that Lys-5 in the context of Src-S3C/S6C interferes with its myristoylation/palmitoylation. This was validated by direct myristoylation and palmitoylation studies, which indicated that the residue at position 5 regulates the membrane interactions of Src versus Fyn. Moreover, the palmitoylation levels correlated with targeting to detergent-resistant membranes (rafts) and to caveolin-1. Palmitoylation-dependent preferential containment of Fyn in rafts may contribute to its lower transformation potential. PMID:27733622

  1. Fixed-base and two-body equations of motion for an Annular Momentum Control Device (AMCD)

    NASA Technical Reports Server (NTRS)

    Groom, N. J.

    1978-01-01

    Fixed base and two body equations of motion for an Annular Momentum Control Device (AMCD) are presented. An AMCD consists of a spinning annular rim which is suspended by noncontacting magnetic bearings and powered by a noncontacting linear electromagnetic motor. The fixed base equations are for a rigid AMCD rim suspended by magnetic bearings attached to a rigid fixed base. The two body equations are for a rigid AMCD rim suspended by magnetic bearings attached to a rigid body spacecraft. The fixed base equations are applicable to any potential ground based AMCD application such as energy storage.

  2. LEDGIN-mediated Inhibition of Integrase-LEDGF/p75 Interaction Reduces Reactivation of Residual Latent HIV.

    PubMed

    Vranckx, Lenard S; Demeulemeester, Jonas; Saleh, Suha; Boll, Annegret; Vansant, Gerlinde; Schrijvers, Rik; Weydert, Caroline; Battivelli, Emilie; Verdin, Eric; Cereseto, Anna; Christ, Frauke; Gijsbers, Rik; Debyser, Zeger

    2016-06-01

    Persistence of latent, replication-competent Human Immunodeficiency Virus type 1 (HIV-1) provirus is the main impediment towards a cure for HIV/AIDS (Acquired Immune Deficiency Syndrome). Therefore, different therapeutic strategies to eliminate the viral reservoirs are currently being explored. We here propose a novel strategy to reduce the replicating HIV reservoir during primary HIV infection by means of drug-induced retargeting of HIV integration. A novel class of integration inhibitors, referred to as LEDGINs, inhibit the interaction between HIV integrase and the LEDGF/p75 host cofactor, the main determinant of lentiviral integration site selection. We show for the first time that LEDGF/p75 depletion hampers HIV-1 reactivation in cell culture. Next we demonstrate that LEDGINs relocate and retarget HIV integration resulting in a HIV reservoir that is refractory to reactivation by different latency-reversing agents. Taken together, these results support the potential of integrase inhibitors that modulate integration site targeting to reduce the likeliness of viral rebound.

  3. Determination of aminoglycoside residues in kidney and honey samples by hydrophilic interaction chromatography-tandem mass spectrometry.

    PubMed

    Kumar, Praveen; Rúbies, Antoni; Companyó, Ramon; Centrich, Francesc

    2012-10-01

    Two methods based on liquid chromatography-tandem mass spectrometry were developed for the determination of ten aminoglycosides (streptomycin, dihydrostreptomycin, spectinomycin, apramycin, paromomycin, kanamycin A, gentamycin C1, gentamycin C2/C2a, gentamycin C1a, and neomycin B) in kidney samples from food-producing animals and in honey samples. The methods involved extraction with an aqueous solution (for the kidney samples) or sample dissolution in water (for the honey samples), solid-phase extraction with a weak cation exchange cartridge and injection of the eluate into a liquid chromatography-tandem mass spectrometry system. A zwitterionic hydrophilic interaction chromatography column was used for separation of aminoglycosides and a triple quadrupole mass analyzer was used for detection. The methods were validated according to Decision 2002/657/EC. The limits of quantitation ranged from 2 to 125 μg/kg in honey and 25 to 264 μg/kg in the kidney samples. Interday precision (RSD%) ranged from 6 to 26% in honey and 2 to 21% in kidney. Trueness, expressed as the percentage of error, ranged from 7 to 20% in honey and 1 to 11% in kidney.

  4. Intra-subunit residue interactions from the protein surface to the active site of glutathione S-transferase AdGSTD3-3 impact on structure and enzyme properties.

    PubMed

    Wongtrakul, Jeerang; Sramala, Issara; Prapanthadara, La-aied; Ketterman, Albert J

    2005-03-01

    Structural residues are one of the major factors that modulate the catalytic specificity as well as having a role in stability of the glutathione S-transferases (GST). To understand how residues remote from the active site can affect enzymatic properties, four mutants, His144Ala, Val147Leu, Val147Ala and Arg96Ala, were generated. The selected residues appear to be in a putative intra-subunit interaction pathway from the exterior Asp150 to the active site Arg66 of AdGSTD3-3. The analysis of the four mutants suggested that the interaction formed between Asp150 and His144 is required for the packing of the hydrophobic core in domain 2. Mutations of both Asp150 and His144 impacted upon enzymatic properties. Two Val147 mutants also showed contribution to packing and support of the N-capping box motif by demonstrating shorter half-lives. The planar guanidinium of Arg96 is in a stacked geometry with the face of the aromatic ring of Phe140 in a cation-pi interaction. The Arg96 also interacts with several other residues one of which, Asp100, is in the active site. These interactions restrict movement of the residues in this region and as the data demonstrates when Arg96 is changed have dramatic impact on stability and enzyme properties. These findings indicate the significance of the roles played by residue interactions which can cause conformational changes and thereby influence the catalytic activity and stability of an enzyme.

  5. The effect of cholesterol on the long-range network of interactions established among sea anemone Sticholysin II residues at the water-membrane interface.

    PubMed

    García-Linares, Sara; Alm, Ida; Maula, Terhi; Gavilanes, José G; Slotte, Johan Peter; Martínez-Del-Pozo, Álvaro

    2015-03-25

    Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol.

  6. The increase in positively charged residues in cecropin D-like Galleria mellonella favors its interaction with membrane models that imitate bacterial membranes.

    PubMed

    Oñate-Garzón, José; Ausili, Alessio; Manrique-Moreno, Marcela; Torrecillas, Alejandro; Aranda, Francisco J; Patiño, Edwin; Gomez-Fernández, Juan C

    2017-09-01

    A comparative study of three synthetic peptides, namely neutral Cecropin D-like G. mellonella (WT) and two cationic peptides derived from its sequence, ΔM1 (+5) and ΔM2 (+9) is reported in this work. The influence of charge on the interactions between peptides and membranes and its effect on phase were studied by calorimetric assays. Differential scanning calorimetry (DSC) showed that ΔM2 peptide showed the strongest effect when the membrane contained phosphatidylcholine (PC) and phosphatidylglycerol (PG), increasing membrane fluidization. Fourier transform infrared spectroscopy (FTIR) was used to determine lipid segregation in the presence of peptides. When WT and ΔM1 bound to model membrane containing PG and PC (1:1 molar ratio) a separation of both lipids was observed. Meanwhile, ΔM2 peptide also induced a demixing of PG-peptide rich domains separated from PC. FTIR experiments also suggested that the presence of ΔM1 and ΔM2 peptides increased lipid carbonyl group hydration in DMPG membrane fluid phase, However, hydration at the interface level in fluid phase was notably increased in the presence of WT and ΔM1 peptides in DMPC/DMPG. Overall the increase in positively charged residues favors the interaction of the peptides with the negatively charged membrane and its perturbation. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor.

    PubMed Central

    Cornelis, S; Plaetinck, G; Devos, R; Van der Heyden, J; Tavernier, J; Sanderson, C J; Guisez, Y; Fiers, W

    1995-01-01

    The receptor for interleukin-5 (IL-5) is composed of two different subunits. The IL-5 receptor alpha (IL-5R alpha) is required for ligand-specific binding while association with the beta-chain results in increased binding affinity. Murine IL-5 (mIL-5) has similar activity on human and murine cells, whereas human IL-5 (hIL-5) has marginal activity on murine cells. We found that the combined substitution of K84 and N108 on hIL-5 by their respective murine counterpart yields a molecule which is as potent as mIL-5 for growth stimulation of a murine cell line. Since the unidirectional species specificity is due only to the interaction with the IL-5R alpha subunit, we have used chimeric IL-5R alpha molecules to define regions of hIL-5R alpha involved in species-specific hIL-5 ligand binding. We found that this property is largely determined by the NH2-terminal module of hIL-5R alpha, and detailed analysis defined D56 and to a lesser extent E58 as important for binding. Moreover, two additional residues, D55 and Y57, were identified by alanine scanning mutagenesis within the same region. Based on the observed homology between the NH2-terminal module and the membrane proximal (WSXWS-containing) module of hIL-5R alpha we located this stretch of four amino acid residues (D55, D56, Y57 and E58) in the loop region that connects the C and D beta-strands on the proposed tertiary structure of the NH2-terminal module.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:7628440

  8. Residual Cap

    NASA Image and Video Library

    2006-05-10

    This MOC image shows a summertime view of the south polar residual cap of Mars. In this image, mesas composed largely of solid carbon dioxide are separated from one another by irregularly-shaped depressions

  9. Pump-Probe Spectroscopy of Two-Body Correlations in Ultracold Gases

    SciTech Connect

    Koch, Christiane P.; Kosloff, Ronnie

    2009-12-31

    We suggest pump-probe spectroscopy to study pair correlations that determine the many-body dynamics in weakly interacting, dilute ultracold gases. A suitably chosen, short laser pulse depletes the pair density locally, creating a 'hole' in the electronic ground state. The dynamics of this nonstationary pair density is monitored by a time-delayed probe pulse. The resulting transient signal allows us to spectrally decompose the hole and to map out the pair correlation function.

  10. A highly conserved interaction involving the middle residue of the SXN active-site motif is crucial for function of class B penicillin-binding proteins: mutational and computational analysis of PBP 2 from N. gonorrhoeae.

    PubMed

    Tomberg, Joshua; Temple, Brenda; Fedarovich, Alena; Davies, Christopher; Nicholas, Robert A

    2012-04-03

    Insertion of an aspartate residue at position 345a in penicillin-binding protein 2 (PBP 2), which lowers the rate of penicillin acylation by ~6-fold, is commonly observed in penicillin-resistant strains of Neisseria gonorrhoeae. Here, we show that insertions of other amino acids also lower the penicillin acylation rate of PBP 2, but none supported growth of N. gonorrhoeae, indicating loss of essential transpeptidase activity. The Asp345a mutation likely acts by altering the interaction between its adjacent residue, Asp346, in the β2a-β2d hairpin loop and Ser363, the middle residue of the SXN active site motif. Because the adjacent aspartate creates ambiguity in the position of the insertion, we also examined if insertions at position 346a could confer decreased susceptibility to penicillin. However, only aspartate insertions were identified, indicating that only an Asp-Asp couple can confer resistance and retain transpeptidase function. The importance of the Asp346-Ser363 interaction was assessed by mutation of each residue to Ala. Although both mutants lowered the acylation rate of penicillin G by 5-fold, neither could support growth of N. gonorrhoeae, again indicating loss of transpeptidase function. Interaction between a residue in the equivalent of the β2a-β2d hairpin loop and the middle residue of the SXN motif is observed in crystal structures of other Class B PBPs, and its importance is also supported by multisequence alignments. Overall, these results suggest that this conserved interaction can be manipulated (e.g., by insertion) to lower the acylation rate by β-lactam antibiotics and increase resistance, but only if essential transpeptidase activity is preserved.

  11. Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel.

    PubMed

    Carrasquel-Ursulaez, Willy; Contreras, Gustavo F; Sepúlveda, Romina V; Aguayo, Daniel; González-Nilo, Fernando; González, Carlos; Latorre, Ramón

    2015-01-01

    Large-conductance Ca(2+)- and voltage-activated K(+) channel (BK) open probability is enhanced by depolarization, increasing Ca(2+) concentration, or both. These stimuli activate modular voltage and Ca(2+) sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca(2+), profoundly hinders channel opening while showing only minor effects on the voltage sensor active-resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca(2+) binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open-closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open-closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations. © 2015 Carrasquel-Ursulaez et al.

  12. Finite-element analysis to determine effect of monolimb flexibility on structural strength and interaction between residual limb and prosthetic socket.

    PubMed

    Lee, Winson C C; Zhang, Ming; Boone, David A; Contoyannis, Bill

    2004-01-01

    Monolimb refers to a kind of transtibial prostheses having the socket and shank molded into one piece of thermoplastic material. One of its characteristics is that the shank is made of a material that can deform during walking, which can simulate ankle joint motion to some extent. Changes in shank geometry can alter the stress distribution within the monolimb and at the residual limb-socket interface and, respectively, affect the deformability and structural integrity of the prosthesis and comfort perceived by amputees. This paper describes the development of a finite-element model for the study of the structural behavior of monolimbs with different shank designs and the interaction between the limb and socket during walking. The von Mises stress distributions in monolimbs with different shank designs at different walking phases are reported. With the use of distortion energy theory, possible failure was predicted. The effect of the stiffness of the monolimb shanks on the stress distribution at the limb-socket interface was studied. The results show a trend--the peak stress applied to the limb was lowered as the shank stiffness decreased. This information is useful for future monolimb optimization.

  13. Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides.

    PubMed Central

    Beroza, P; Fredkin, D R; Okamura, M Y; Feher, G

    1991-01-01

    We used Monte Carlo methods to treat statistical problem of electrostatic interactions among many titrating amino acids and applied these methods to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides, including all titrating sites. We computed the average protonation of residues as a function of pH from an equilibrium distribution of states generated by random sampling. Electrostatic energies were calculated from a finite difference solution to the linearized Poisson-Boltzmann equation using the coordinates from solved protein structures. For most calculations we used the Metropolis algorithm to sample protonation states; for strongly coupled sites, we substantially reduced sampling errors by using a modified algorithm that allows multiple site transitions. The Monte Carlo method agreed with calculations for a small test system, lysozyme, for which the complete partition function was calculated. We also calculated the pH dependence of the free energy change associated with electron transfer from the primary to the secondary quinone in the photosynthetic reaction center. The shape of the resulting curve agreed fairly well with experiment, but the proton uptake from which the free energy was calculated agreed only to within a factor of two with the observed values. We believe that this discrepancy resulted from errors in the individual electrostatic energy calculations rather than from errors in the Monte Carlo sampling. PMID:2062860

  14. Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel

    PubMed Central

    Carrasquel-Ursulaez, Willy; Contreras, Gustavo F.; Sepúlveda, Romina V.; Aguayo, Daniel; González-Nilo, Fernando

    2015-01-01

    Large-conductance Ca2+- and voltage-activated K+ channel (BK) open probability is enhanced by depolarization, increasing Ca2+ concentration, or both. These stimuli activate modular voltage and Ca2+ sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca2+, profoundly hinders channel opening while showing only minor effects on the voltage sensor active–resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca2+ binding from voltage sensor activation and voltage sensor activation from channel opening. However, the presence of a bulky and more hydrophobic amino acid in the F380 position (F380W) increases the intrinsic open–closed equilibrium, weakening the coupling between both sensors with the pore domain. Based on these functional experiments and molecular dynamics simulations, we propose that F380 interacts with another S6 hydrophobic residue (L377) in contiguous subunits. This pair forms a hydrophobic ring important in determining the open–closed equilibrium and, like an integration node, participates in the communication between sensors and between the sensors and pore. Moreover, because of its effects on open probabilities, the F380A mutant can be used for detailed voltage sensor experiments in the presence of permeant cations. PMID:25548136

  15. Variola Virus IL-18 Binding Protein Interacts with Three Human IL-18 Residues That Are Part of a Binding Site for Human IL-18 Receptor Alpha Subunit

    PubMed Central

    Meng, Xiangzhi; Leman, Michael; Xiang, Yan

    2007-01-01

    Interleukin-18 (IL-18) plays an important role in host defense against microbial pathogens. Many poxviruses encode homologous IL-18 binding proteins (IL-18BP) that neutralize IL-18 activity. Here, we examined whether IL-18BP neutralizes IL-18 activity by binding to the same region of IL-18 where IL-18 receptor (IL-18R) binds. We introduced alanine substitutions to known receptor binding sites of human IL18, and found that only the substitution of Leu5 reduced the binding affinity of IL-18 with IL-18BP of variola virus (varvIL-18BP) by more than 4-fold. The substitutions of Lys53 and Ser55, which were not previously known to be part of the receptor binding site but that are spatially adjacent to Leu5, reduced the binding affinity to varvIL-18BP by approximately 100- and 7-fold, respectively. These two substitutions also reduced the binding affinity with human IL-18R alpha subunit (hIL-18Rα) by 4- and 2-fold, respectively. Altogether, our data shows that varvIL-18BP prevents IL-18 from binding to IL-18R by interacting with three residues that are part of the binding site for hIL-18Rα. PMID:16979683

  16. Two-body pion absorption on {sup 3}He at threshold

    SciTech Connect

    Lee, T.S.H.; Kiang, L.L.; Riska, D.O.

    1995-08-01

    We showed that a drastic reduction of the ratio of the rates of the reactions {sup 3}He({pi}{sup -},nn) and {sup 3}He({pi}{sup -},np) for stopped pions is obtained once the effect of the short-range two-nucleon components of the axial charge operator for nuclear systems is taken into account. In a calculation using realistic models of nucleon-nucleon interactions in the construction of these short-range components of the axial charge operator, the predicted ratios can be brought to within 10-20% of the empirical value. A paper describing our results was published.

  17. Detailed description of exclusive muon capture rates using realistic two-body forces

    NASA Astrophysics Data System (ADS)

    Giannaka, P. G.; Kosmas, T. S.

    2015-07-01

    Starting from state-by-state calculations of exclusive rates of the ordinary muon capture, we evaluated total μ- capture rates for a set of light- and medium-weight nuclear isotopes. We employed a version of the proton-neutron quasiparticle random-phase approximation (p n -QRPA, for short) which uses as realistic nuclear forces the Bonn C-D one-boson exchange potential. Special attention was paid on the percentage contribution to the total μ- capture rate of specific low-spin multipolarities resulting by summing over the corresponding multipole transitions. The nuclear method used offers the possibility of estimating separately the individual contributions to the total and partial rates of the polar-vector and axial-vector components of the weak-interaction Hamiltonian for each accessible final state of the daughter nucleus. One of our main goals is to provide a reliable description of the charge-changing transitions matrix elements entering the description of other similar semileptonic nuclear processes like the charged-current neutrino-nucleus reactions, the electron capture on nuclei, the single β±-decay mode, etc., which play important role in currently interesting laboratory and astrophysical applications like the neutrino detection through lepton-nucleus interaction probes and neutrino nucleosynthesis. Such results can also be useful in various ongoing muon capture experiments at Paul Scherrer Institute (PSI), Fermilab, Japan Proton Accelerator Research Complex, and Research Center for Nuclear Physics, Osaka University.

  18. The regulatory subunit of Escherichia coli aspartate carbamoyltransferase may influence homotropic cooperativity and heterotropic interactions by a direct interaction with the loop containing residues 230-245 of the catalytic chain.

    PubMed Central

    Newton, C J; Kantrowitz, E R

    1990-01-01

    A recent x-ray structure of aspartate carbamoyltransferase (carbamoyl-phosphate: L-aspartate carbamoyl-transferase, EC 2.1.3.2) with phosphonoacetamide bound [Gouaux, J. E. & Lipscomb, W. N. (1990) Biochemistry 29, 389-402] shows an interaction between Asp-236 of the catalytic chain and Lys-143 of the regulatory chain. Asp-236 is part of the loop containing residues 230-245 (240s) of the catalytic chain that undergoes a significant conformational change between the tight and the relaxed states of the enzyme. Furthermore, side-chain interactions between the 240s loop and other portions of the enzyme have been shown to be important for the low activity and low affinity of the tight state and the high activity and high affinity of the relaxed state. To determine whether the intersubunit link between Lys-143 of the regulatory chain and Asp-236 of the catalytic chain is important for either homotropic cooperativity and/or the heterotropic interactions in aspartate carbamoyltransferase, site-specific mutagenesis was used to replace Asp-236 with alanine. The mutant enzyme exhibits full activity and a loss of both homotropic cooperativity and heterotropic interactions. Furthermore, the aspartate concentration at half the maximal observed specific activity is reduced by approximately 8-fold. The mutant enzyme exhibits normal thermal stability but drastically altered reactivity toward p-hydroxymercuribenzoate. The catalytic subunit of the mutant and wild-type enzymes have very similar properties. These results, in conjunction with previous experiments, suggest that the intersubunit link involving Asp-236 is involved in the stabilization of the 240s loop in its tight-state position and that the regulatory subunits exert their effect on the catalytic subunits by influencing the position of the 240s loop. PMID:2179954

  19. Two-body coordinate system generation using body-fitted coordinate system and complex variable transformation. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Long, W. S.

    1977-01-01

    Attempts are made to generate acceptable coordinate systems for two-body configurations. The first method to be tried was to use the body-fitted coordinate system technique to obtain the best system. This technique alone did not produce very good results, so another approach was investigated. This new approach involved using a combination of the body fitted coordinate system procedure and a complex variable transformation method that was used successfully in conformal mapping.

  20. Identification of Amino Acid Residues in Fibroblast Growth Factor 14 (FGF14) Required for Structure-Function Interactions with Voltage-gated Sodium Channel Nav1.6.

    PubMed

    Ali, Syed R; Singh, Aditya K; Laezza, Fernanda

    2016-05-20

    The voltage-gated Na(+) (Nav) channel provides the basis for electrical excitability in the brain. This channel is regulated by a number of accessory proteins including fibroblast growth factor 14 (FGF14), a member of the intracellular FGF family. In addition to forming homodimers, FGF14 binds directly to the Nav1.6 channel C-tail, regulating channel gating and expression, properties that are required for intrinsic excitability in neurons. Seeking amino acid residues with unique roles at the protein-protein interaction interface (PPI) of FGF14·Nav1.6, we engineered model-guided mutations of FGF14 and validated their impact on the FGF14·Nav1.6 complex and the FGF14:FGF14 dimer formation using a luciferase assay. Divergence was found in the β-9 sheet of FGF14 where an alanine (Ala) mutation of Val-160 impaired binding to Nav1.6 but had no effect on FGF14:FGF14 dimer formation. Additional analysis revealed also a key role of residues Lys-74/Ile-76 at the N-terminal of FGF14 in the FGF14·Nav1.6 complex and FGF14:FGF14 dimer formation. Using whole-cell patch clamp electrophysiology, we demonstrated that either the FGF14(V160A) or the FGF14(K74A/I76A) mutation was sufficient to abolish the FGF14-dependent regulation of peak transient Na(+) currents and the voltage-dependent activation and steady-state inactivation of Nav1.6; but only V160A with a concomitant alanine mutation at Tyr-158 could impede FGF14-dependent modulation of the channel fast inactivation. Intrinsic fluorescence spectroscopy of purified proteins confirmed a stronger binding reduction of FGF14(V160A) to the Nav1.6 C-tail compared with FGF14(K74A/I76A) Altogether these studies indicate that the β-9 sheet and the N terminus of FGF14 are well positioned targets for drug development of PPI-based allosteric modulators of Nav channels.

  1. Identification of Amino Acid Residues in Fibroblast Growth Factor 14 (FGF14) Required for Structure-Function Interactions with Voltage-gated Sodium Channel Nav1.6*

    PubMed Central

    Ali, Syed R.; Singh, Aditya K.; Laezza, Fernanda

    2016-01-01

    The voltage-gated Na+ (Nav) channel provides the basis for electrical excitability in the brain. This channel is regulated by a number of accessory proteins including fibroblast growth factor 14 (FGF14), a member of the intracellular FGF family. In addition to forming homodimers, FGF14 binds directly to the Nav1.6 channel C-tail, regulating channel gating and expression, properties that are required for intrinsic excitability in neurons. Seeking amino acid residues with unique roles at the protein-protein interaction interface (PPI) of FGF14·Nav1.6, we engineered model-guided mutations of FGF14 and validated their impact on the FGF14·Nav1.6 complex and the FGF14:FGF14 dimer formation using a luciferase assay. Divergence was found in the β-9 sheet of FGF14 where an alanine (Ala) mutation of Val-160 impaired binding to Nav1.6 but had no effect on FGF14:FGF14 dimer formation. Additional analysis revealed also a key role of residues Lys-74/Ile-76 at the N-terminal of FGF14 in the FGF14·Nav1.6 complex and FGF14:FGF14 dimer formation. Using whole-cell patch clamp electrophysiology, we demonstrated that either the FGF14V160A or the FGF14K74A/I76A mutation was sufficient to abolish the FGF14-dependent regulation of peak transient Na+ currents and the voltage-dependent activation and steady-state inactivation of Nav1.6; but only V160A with a concomitant alanine mutation at Tyr-158 could impede FGF14-dependent modulation of the channel fast inactivation. Intrinsic fluorescence spectroscopy of purified proteins confirmed a stronger binding reduction of FGF14V160A to the Nav1.6 C-tail compared with FGF14K74A/I76A. Altogether these studies indicate that the β-9 sheet and the N terminus of FGF14 are well positioned targets for drug development of PPI-based allosteric modulators of Nav channels. PMID:26994141

  2. Electrodynamic two-body problem for prescribed initial data on a straight line

    NASA Astrophysics Data System (ADS)

    Deckert, D.-A.; Hinrichs, G.

    2016-05-01

    Electrodynamic interaction between point charges can be described by a system of ODEs involving advanced and retarded delays - the so-called Fokker-Schwarzschild-Tetrode (FST) equations. In special situations, approximate equations can be derived which are purely retarded. Upon omission of the terms describing radiation friction, these are called Synge equations. In both cases, few mathematical results are available on existence and uniqueness of solutions. We investigate the situation of two like point-charges in 3 + 1 space-time dimensions restricted to motion on a straight line. We give a priori estimates on the asymptotic motion and, using a Leray-Schauder argument, prove: 1) Existence of solutions to the FST equations on the future or past half-line given finite trajectory segments; 2) Global existence of the Synge equations for Cauchy data; 3) Global existence of a FST toy model. Furthermore, we give a sufficient criterion that uniquely distinguishes solutions by means of finite trajectory segments.

  3. Geometrical crossover in two-body systems in a magnetic field

    NASA Astrophysics Data System (ADS)

    Cerkaski, M.; Nazmitdinov, R. G.

    2013-08-01

    An algebraic approach is formulated in the harmonic approximation to describe a dynamics of two-fermion systems, confined in a three-dimensional axially symmetric parabolic potential, in an external magnetic field. The fermion interaction is considered in the form \\mathscr {U}_{M}( r )= \\alpha _{ M}\\,r^{-M} (αM > 0, M > 0). The formalism of a semisimple Lie group is applied to analyse symmetries of the considered system. Explicit algebraic expressions are derived in terms of the system's parameters and the magnetic field strength to trace the evolution of the equilibrium shape. It is predicted that the interplay of classical and quantum correlations may lead to a quantum shape transition from a lateral to a vertical localization of fermions in the confined system. The analytical results demonstrate a good agreement with the numerical results for two-electron quantum dots in the magnetic field, when classical correlations dominate in the dynamics.

  4. Development of a two-body wet abrasion test method with attention to the effects of reused abradant

    SciTech Connect

    Blau, Peter Julian; Dehoff, Ryan R

    2012-01-01

    Abrasive wear is among the most common and costliest causes for material wastage, and it occurs in many forms. A simple method has been developed to quantify the response of metals and alloys to two-body wet abrasion. A metallographic polishing machine was modified to create a disk-on-flat sliding test rig. Adhesive-backed SiC grinding papers were used under fixed load and speed to rank the abrasive wear of seven alloy steels, some of which are candidates for drill cones for geothermal drilling. Standardized two-body abrasion tests, like those described in ASTM G132, feed unused abrasive into the contact; however, the current work investigated whether useful rankings could still be obtained with a simpler testing configuration in which specimens repeatedly slide on the same wear path under water-lubricated conditions. Tests using abrasive grit sizes of 120 and 180 resulted in the same relative ranking of the alloys although the coarser grit produced more total wear. Wear decreased when the same abrasive disk was re-used for up to five runs, but the relative rankings of the steels remained the same. This procedure was presented to ASTM Committee G2 on Wear and Erosion as a potential standard test for wet two-body abrasive wear.

  5. Structure-Based Network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators of Structural Stability and Allosteric Interactions

    PubMed Central

    James, Kevin A.; Verkhivker, Gennady M.

    2014-01-01

    The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced “superacceptor” activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the

  6. A 20-residue peptide of the inner membrane protein OutC mediates interaction with two distinct sites of the outer membrane secretin OutD and is essential for the functional type II secretion system in Erwinia chrysanthemi.

    PubMed

    Login, Frédéric H; Fries, Markus; Wang, Xiaohui; Pickersgill, Richard W; Shevchik, Vladimir E

    2010-05-01

    The type II secretion system (T2SS) is widely exploited by proteobacteria to secrete enzymes and toxins involved in bacterial survival and pathogenesis. The outer membrane pore formed by the secretin OutD and the inner membrane protein OutC are two key components of the secretion complex, involved in secretion specificity. Here, we show that the periplasmic regions of OutC and OutD interact directly and map the interaction site of OutC to a 20-residue peptide named OutCsip (secretin interacting peptide, residues 139-158). This peptide interacts in vitro with two distinct sites of the periplasmic region of OutD, one located on the N0 subdomain and another overlapping the N2-N3' subdomains. The two interaction sites of OutD have different modes of binding to OutCsip. A single substitution, V143S, located within OutCsip prevents its interaction with one of the two binding sites of OutD and fully inactivates the T2SS. We show that the N0 subdomain of OutD interacts also with a second binding site within OutC located in the region proximal to the transmembrane segment. We suggest that successive interactions between these distinct regions of OutC and OutD may have functional importance in switching the secretion machine.

  7. Positively Charged Residues at the Five-Fold Symmetry Axis of Cell Culture-Adapted Foot-and-Mouth Disease Virus Permit Novel Receptor Interactions

    PubMed Central

    Berryman, Stephen; Clark, Stuart; Kakker, Naresh K.; Silk, Rhiannon; Seago, Julian; Wadsworth, Jemma; Chamberlain, Kyle; Knowles, Nick J.

    2013-01-01

    Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV. In cell culture, a virus with the capsid of the A/Turkey/2/2006 field isolate gained the ability to infect CHO and HS-deficient CHO cells as a result of a single glutamine (Q)-to-lysine (K) substitution at VP1-110 (VP1-Q110K). Using site-directed mutagenesis, the introduction of lysine at this same site also resulted in an acquired ability to infect CHO cells by type O and Asia-1 FMDV. However, this ability appeared to require a second positively charged residue at VP1-109. CHO cells express two RGD-binding integrins (α5β1 and αvβ5) that, although not used by FMDV, have the potential to be used as receptors; however, viruses with the VP1-Q110K substitution did not use these integrins. In contrast, the VP1-Q110K substitution appeared to result in enhanced interactions with αvβ6, which allowed a virus with KGE in place of the normal RGD integrin-binding motif to use αvβ6 as a receptor. Thus, our results confirmed the existence of nonintegrin, non-HS receptors for FMDV on CHO cells and revealed a novel, non-RGD-dependent use of αvβ6 as a receptor. The introduction of lysine at VP1-110 may allow for cell culture adaptation of FMDV by design, which may prove useful for vaccine manufacture when cell culture adaptation proves intractable. PMID:23740982

  8. Binding of amino acid side chains to preformed cavities: interaction of serine proteinases with turkey ovomucoid third domains with coded and noncoded P1 residues.

    PubMed Central

    Bigler, T. L.; Lu, W.; Park, S. J.; Tashiro, M.; Wieczorek, M.; Wynn, R.; Laskowski, M.

    1993-01-01

    In the association of serine proteinases with their cognate substrates and inhibitors an important interaction is the fitting of the P1 side chain of the substrate or inhibitor into a preformed cavity of the enzyme called the S1 pocket. In turkey ovomucoid third domain, which is a canonical protein proteinase inhibitor, the P1 residue is Leu18. Here we report the values of equilibrium constants, Ka, for turkey ovomucoid third domain and 13 additional Leu18X variants with six serine proteinases: bovine alpha chymotrypsin A, porcine pancreatic elastase, subtilisin Carlsberg, Streptomyces griseus proteinases A and B, and human leukocyte elastase. Eight of the Xs are coded amino acids: Ala, Ser, Val, Met, Gln, Glu, Lys, and Phe, and five are noncoded: Abu, Ape, Ahx, Ahp, and Hse. They were chosen to simplify the interamino acid comparisons. In the homologous series of straight-chain side chains Ala, Abu, Ape, Ahx, Ahp, free energy of binding decreases monotonically with the side-chain length for chymotrypsin with large binding pocket, but even for this enzyme shows curvature. For the two S. griseus enzymes a minimum appears to be reached at Ahp. A minimum is clearly evident for the two elastases, where increasing the side-chain length from Ahx to Ahp greatly weakens binding, but much more so for the apparently more rigid pancreatic enzyme than for the more flexible leukocyte enzyme. beta-Branching (Ape/Val) is very deleterious for five of the six enzymes; it is only slightly deleterious for the more flexible human leukocyte elastase. The effect of gamma-branching (Ahx/Leu), of introduction of heteroatoms (Abu/Ser), (Ape/Hse), and (Ahx/Met), and of introduction of charge (Gln/Glu) and (Ahp/Lys) are tabulated and discussed. An important component of the free energy of interaction is the distortion of the binding pocket by bulky or branched side chains. Most of the variants studied were obtained by enzymatic semisynthesis. X18 variants of the 6-18 peptide GlyNH2 were

  9. Functional roles of the N-terminal amino acid residues in the Mn(II)-L-malate binding and subunit interactions of pigeon liver malic enzyme.

    PubMed

    Chou, W Y; Huang, S M; Chang, G G

    1997-10-01

    Pigeon liver malic enzyme has an N-terminal amino acid sequence of Met-Lys-Lys-Gly-Tyr-Glu-. In this work, various mutants of the enzyme with individual or combinational deletion (delta) or substitution at these amino acids were constructed and functionally expressed in Escherichia coli cells. A major protein band corresponding to an Mr of approximately 65000 was observed for all recombinant enzymes in sodium dodecyl sulfate polyacrylamide gel electrophoresis. However, when examining by polyacrylamide gel electrophoresis under native conditions, the recombinant enzymes were found to possess a tetrameric structure with Mr approximately 260000 or a mixture of tetramers and dimers with the exception of delta(K2K3G4) and delta(1-16) mutants, which existed exclusively as dimers at the protein concentration we employed. K3A and K3E also dissociated substantially. K(2,3)A was a tetramer but K(2,3)E essentially existed as dimers. All tetramers and dimers were enzymatically active in the gels. All mutants displayed a similar apparent Km value for NADP+. The apparent Km for L-malate and Mn(II), on the other hand, was increased by 4-27-fold for the delta(K2/K3) and the delta(1-16) mutants. The small binding affinity of delta(K2/K3) with Mn(II)-L-malate was specific. With additional deletion at positions 3 and/or 4, the delta(K2K3), delta(K2G4/K3G4) or delta(K2K3G4) mutants exhibited similar kinetic properties for the wild type. The lysine residues at the positions 2 or 3 seem to be crucial for the correct active site conformation. The results indicate that the N-terminus of malic enzyme is located at the Mn(II)-L-malate binding domain of the active center and is also near the subunit's interface. These results were interpreted with our asymmetric double-dimer model for the enzyme in which the N-terminus was involved in the head-to-tail monomer-monomer interactions but not the dimer-dimer interactions.

  10. Effects of energy supply on leucine utilization by growing steers at two body weights.

    PubMed

    Schroeder, G F; Titgemeyer, E C; Moore, E S

    2007-12-01

    The effects of energy supplementation on Leu utilization in growing steers were evaluated in 2 experiments by using 6 ruminally cannulated Holstein steers. In Exp. 1, steers (initial BW = 150 +/- 7 kg) were limit-fed (2.3 kg of DM/d) a diet based on soybean hulls and received a basal ruminal infusion of 100 g of acetate/d, 75 g of propionate/d, and 75 g of butyrate/d, as well as abomasal infusions of 200 g of glucose/d and a mixture (215 g/d) containing all essential AA except Leu. Treatments were arranged as a 3 x 2 factorial, with 3 amounts of Leu infused abomasally (0, 4, and 8 g/d) and supplementation of diets with 2 amounts of energy (0 and 1.9 Mcal/d of GE). Supplemental energy was supplied by ruminal infusion of 100 g of acetate/ d, 75 g of propionate/d, and 75 g of butyrate/d, as well as abomasal infusion of 200 g of glucose/d to provide energy to the animal without affecting the microbial protein supply. When no supplemental energy was provided, Leu supplementation increased N balance, with no difference between 4 and 8 g/d of Leu (24.5, 27.0, and 27.3 g/d for 0, 4, and 8 g/d of Leu), but when additional energy was supplied, N retention increased linearly in response to Leu (25.6, 28.5, and 31.6 g/d for 0, 4, and 8 g/d of Leu; Leu x energy interaction, P = 0.06). The changes in N balance were the result of changes in urinary N excretion. The greater Leu retentions in response to energy supplementation when Leu was the most limiting nutrient indicate that energy supplementation improved the true efficiency of Leu utilization. In addition, supplemental energy increased the gross efficiency of Leu utilization when the Leu supply was not limiting by increasing the maximal rates of protein deposition. Experiment 2 was similar to Exp. 1, but steers had an initial BW of 275 +/- 12 kg and were limit-fed at 3.6 kg of DM/d. Retention of N was not affected (P = 0.22) by Leu supplementation, indicating that Leu did not limit protein deposition. Energy supply increased

  11. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor.

    PubMed

    Assadi-Porter, Fariba M; Maillet, Emeline L; Radek, James T; Quijada, Jeniffer; Markley, John L; Max, Marianna

    2010-05-14

    The sweet protein brazzein [recombinant protein with sequence identical with the native protein lacking the N-terminal pyroglutamate (the numbering system used has Asp2 as the N-terminal residue)] activates the human sweet receptor, a heterodimeric G-protein-coupled receptor composed of subunits Taste type 1 Receptor 2 (T1R2) and Taste type 1 Receptor 3 (T1R3). In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: site 1 (Loop43), site 2 (N- and C-termini and adjacent Glu36, Loop33), and site 3 (Loop9-19). Basic residues in site 1 and acidic residues in site 2 were essential for positive responses from each assay. Mutation of Y39A (site 1) greatly reduced positive responses. A bulky side chain at position 54 (site 2), rather than a side chain with hydrogen-bonding potential, was required for positive responses, as was the presence of the native disulfide bond in Loop9-19 (site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus flytrap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in brazzein response. The exception, hT1R2 (human T1R2 subunit of the sweet receptor):R217A/hT1R3 (human T1R3 subunit of the sweet receptor), which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase

  12. Elimination of secular terms from the differential equations for the elements of perturbed two-body motion

    NASA Technical Reports Server (NTRS)

    Bond, Victor R.; Fraietta, Michael F.

    1991-01-01

    In 1961, Sperling linearized and regularized the differential equations of motion of the two-body problem by changing the independent variable from time to fictitious time by Sundman's transformation (r = dt/ds) and by embedding the two-body energy integral and the Laplace vector. In 1968, Burdet developed a perturbation theory which was uniformly valid for all types of orbits using a variation of parameters approach on the elements which appeared in Sperling's equations for the two-body solution. In 1973, Bond and Hanssen improved Burdet's set of differential equations by embedding the total energy (which is a constant when the potential function is explicitly dependent upon time.) The Jacobian constant was used as an element to replace the total energy in a reformulation of the differential equations of motion. In the process, another element which is proportional to a component of the angular momentum was introduced. Recently trajectories computed during numerical studies of atmospheric entry from circular orbits and low thrust beginning in near-circular orbits exhibited numerical instability when solved by the method of Bond and Gottlieb (1989) for long time intervals. It was found that this instability was due to secular terms which appear on the righthand sides of the differential equations of some of the elements. In this paper, this instability is removed by the introduction of another vector integral called the delta integral (which replaces the Laplace Vector) and another scalar integral which removes the secular terms. The introduction of these integrals requires a new derivation of the differential equations for most of the elements. For this rederivation, the Lagrange method of variation of parameters is used, making the development more concise. Numerical examples of this improvement are presented.

  13. Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non-active site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme

    PubMed Central

    Wilderman, P. Ross; Gay, Sean C.; Jang, Hyun-Hee; Zhang, Qinghai; Stout, C. David; Halpert, James R.

    2014-01-01

    SUMMARY Residues located outside of the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability, and drug metabolism. However, contributions of non-active site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue-residue interactions found in crystal structures of P450 2B4 in complex with 4-(4-chlorophenyl)imidazole (4-CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over eleven sites were constructed, expressed in E. coli, and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4-CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D, and E474Q) were chosen for detailed functional analysis. Among these, the Ks of H172F for bifonazole was ~20-times higher than wild type 2B4, and the Ks of L437A for 4-CPI was ~50-times higher than wild type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC), and 7-benzyloxyresorufin (7-BR). H172F was inactive with all three substrates, and L437A did not turn over 7-BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in kcat/KM for each of the three substrates, in some cases up to 50-fold. Concurrent molecular dynamics simulations yield distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function. PMID:22051155

  14. Complete angular distribution measurements of two-body deuteron photodisintegration between 0.5 and 3 GeV

    SciTech Connect

    M. Mirazita; F. Ronchetti; P. Rossi; E. De Sanctis; CLAS Collaboration

    2004-07-12

    Nearly complete angular distributions of the two-body deuteron photodisintegration differential cross section have been measured using the CEBAF Large Acceptance Spectrometer detector and the tagged photon beam at the Thomas Jefferson National Accelerator Facility. The data cover photon energies between 0.5 and 3.0 GeV and center-of-mass proton scattering angles 10{sup o}-160{sup o}. The data show a persistent forward-backward angle asymmetry over the explored energy range, and are well described by the nonperturbative quark gluon string model.

  15. Complete angular distribution measurements of two-body deuteron photodisintegration between 0.5 and 3 GeV

    NASA Astrophysics Data System (ADS)

    Mirazita, M.; Ronchetti, F.; Rossi, P.; de Sanctis, E.; Adams, G.; Ambrozewicz, P.; Anciant, E.; Anghinolfi, M.; Asavapibhop, B.; Audit, G.; Avakian, H.; Bagdasaryan, H.; Ball, J. P.; Barrow, S.; Battaglieri, M.; Beard, K.; Bektasoglu, M.; Bellis, M.; Benmouna, N.; Berman, B. L.; Bertozzi, W.; Bianchi, N.; Biselli, A. S.; Boiarinov, S.; Bonner, B. E.; Bouchigny, S.; Bradford, R.; Branford, D.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Butuceanu, C.; Calarco, J. R.; Carman, D. S.; Carnahan, B.; Chen, S.; Cole, P. L.; Cords, D.; Corvisiero, P.; Crabb, D.; Crannell, H.; Cummings, J. P.; de Vita, R.; Degtyarenko, P. V.; Denizli, H.; Dennis, L.; Deppman, A.; Dharmawardane, K. V.; Dhuga, K. S.; Djalali, C.; Dodge, G. E.; Doughty, D.; Dragovitsch, P.; Dugger, M.; Dytman, S.; Dzyubak, O. P.; Egiyan, H.; Egiyan, K. S.; Elouadrhiri, L.; Empl, A.; Eugenio, P.; Fatemi, R.; Feuerbach, R. J.; Ficenec, J.; Forest, T. A.; Funsten, H.; Gai, M.; Gavalian, G.; Gilad, S.; Gilfoyle, G. P.; Giovanetti, K. L.; Gordon, C. I.; Griffioen, K.; Guidal, M.; Guillo, M.; Guo, L.; Gyurjyan, V.; Hadjidakis, C.; Hakobyan, R. S.; Hardie, J.; Heddle, D.; Hersman, F. W.; Hicks, K.; Hicks, R. S.; Holtrop, M.; Hu, J.; Hyde-Wright, C. E.; Ilieva, Y.; Ito, M. M.; Jenkins, D.; Joo, K.; Kellie, J. D.; Khandaker, M.; Kim, K. Y.; Kim, K.; Kim, W.; Klein, A.; Klein, F. J.; Klimenko, A. V.; Klusman, M.; Kossov, M.; Kramer, L. H.; Kuhn, J.; Kuhn, S. E.; Kuhn, J.; Lachniet, J.; Laget, J. M.; Lawrence, D.; Li, Ji; Lima, A. C.; Livingston, K.; Lukashin, K.; Manak, J. J.; Marchand, C.; McAleer, S.; McCarthy, J.; McNabb, J. W.; Mecking, B. A.; Mehrabyan, S.; Melone, J. J.; Mestayer, M. D.; Meyer, C. A.; Mikhailov, K.; Miskimen, R.; Mokeev, V.; Morand, L.; Morrow, S. A.; Muccifora, V.; Mueller, J.; Mutchler, G. S.; Napolitano, J.; Nasseripour, R.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Niczyporuk, B. B.; Niyazov, R. A.; Nozar, M.; O'Brien, J. T.; O'Rielly, G. V.; Osipenko, M.; Ostrovidov, A.; Park, K.; Pasyuk, E.; Peterson, G.; Philips, S. A.; Pivnyuk, N.; Pocanic, D.; Pogorelko, O.; Polli, E.; Pozdniakov, S.; Preedom, B. M.; Price, J. W.; Prok, Y.; Protopopescu, D.; Qin, L. M.; Raue, B. A.; Riccardi, G.; Ricco, G.; Ripani, M.; Ritchie, B. G.; Rosner, G.; Rowntree, D.; Rubin, P. D.; Sabatié, F.; Salgado, C.; Santoro, J. P.; Sapunenko, V.; Schumacher, R. A.; Serov, V. S.; Sharabian, Y. G.; Shaw, J.; Simionatto, S.; Skabelin, A. V.; Smith, E. S.; Smith, L. C.; Sober, D. I.; Spraker, M.; Stavinsky, A.; Stepanyan, S.; Stokes, B.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Taylor, S.; Tedeschi, D. J.; Thoma, U.; Thompson, R.; Tkabladze, A.; Todor, L.; Tur, C.; Ungaro, M.; Vineyard, M. F.; Vlassov, A. V.; Wang, K.; Weinstein, L. B.; Weller, H.; Weygand, D. P.; Whisnant, C. S.; Wolin, E.; Wood, M. H.; Yegneswaran, A.; Yun, J.; Zhang, B.; Zhou, Z.

    2004-07-01

    Nearly complete angular distributions of the two-body deuteron photodisintegration differential cross section have been measured using the CEBAF Large Acceptance Spectrometer detector and the tagged photon beam at the Thomas Jefferson National Accelerator Facility. The data cover photon energies between 0.5 and 3.0 GeV and center-of-mass proton scattering angles 10° 160° . The data show a persistent forward-backward angle asymmetry over the explored energy range, and are well described by the nonperturbative quark gluon string model.

  16. Conformational changes of trialanine induced by direct interactions between alanine residues and alcohols in binary mixtures of water with glycerol and ethanol.

    PubMed

    Toal, Siobhan; Amidi, Omid; Schweitzer-Stenner, Reinhard

    2011-08-17

    linear correlation, which reflects enthalpy-entropy compensation and a common transition temperature. The latter can be considered an indication of a weak binding between cosolvent and peptide. A comparison of infrared and Raman spectra of trialanine in water and in water-alcohol mixtures indeed reveals a close proximity between aliphatic side chains of alanine residues and alcohol molecules even for 5% (v/v) alcohol-water mixtures. Hence, our results provide the first experimental evidence for direct interactions between, e.g., glycerol and peptides in aqueous solutions, in line with the result of recent calculations by Vagenende et al. (Biochemistry 2009, 48, 11084-11096) but at variance with preferential exclusion theories.

  17. Quasi-two-body decays B(s )→P ρ →P π π in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Li, Ya; Ma, Ai-Jun; Wang, Wen-Fei; Xiao, Zhen-Jun

    2017-03-01

    In this work, we calculate the C P -averaged branching ratios and the direct C P -violating asymmetries of the quasi-two-body decays B(s )→P (ρ →)π π by employing the perturbative QCD (PQCD) approach (here P stands for a light pseudoscalar meson π , K , η or η'). The vector current timelike form factor Fπ, which contains the final-state interactions between the pion pair in the resonant region associated with the P -wave states ρ (770 ) along with the two-pion distribution amplitudes, is employed to describe the interactions between the ρ and the pion pair under the hypothesis of the conserved vector current. We found that (a) the PQCD predictions for the branching ratios and the direct C P -violating asymmetries for most considered B(s )→P (ρ →)π π decays agree with currently available data within errors, (b) for B (B →π0ρ0→π0(π+π-) , the PQCD prediction is much smaller than the measured one, and (c) for the B+→π+(ρ0→)π+π- decay mode, there is a negative C P asymmetry (-27.5-3.7+3.0)% , which agrees with other theoretical predictions but is different in sign from those reported by the BABAR and LHCb Collaborations.

  18. Residues required for Bacillus subtilis PhoP DNA binding or RNA polymerase interaction: alanine scanning of PhoP effector domain transactivation loop and alpha helix 3.

    PubMed

    Chen, Yinghua; Abdel-Fattah, Wael R; Hulett, F Marion

    2004-03-01

    Bacillus subtilis PhoP is a member of the OmpR family of response regulators that activates or represses genes of the Pho regulon upon phosphorylation by PhoR in response to phosphate deficiency. Because PhoP binds DNA and is a dimer in solution independent of its phosphorylation state, phosphorylation of PhoP may optimize DNA binding or the interaction with RNA polymerase. We describe alanine scanning mutagenesis of the PhoP alpha loop and alpha helix 3 region of PhoPC (Val190 to E214) and functional analysis of the mutated proteins. Eight residues important for DNA binding were clustered between Val202 and Arg210. Using in vivo and in vitro functional analyses, we identified three classes of mutated proteins. Class I proteins (PhoP(I206A), PhoP(R210A), PhoP(L209A), and PhoP(H208A)) were phosphorylation proficient and could dimerize but could not bind DNA or activate transcription in vivo or in vitro. Class II proteins (PhoP(H205A) and PhoP(V204A)) were phosphorylation proficient and could dimerize but could not bind DNA prior to phosphorylation. Members of this class had higher transcription activation in vitro than in vivo. The class III mutants, PhoP(V202A) and PhoP(D203A), had a reduced rate of phosphotransfer and could dimerize but could not bind DNA or activate transcription in vivo or in vitro. Seven alanine substitutions in PhoP (PhoP(V190A), PhoP(W191A), PhoP(Y193A), PhoP(F195A), PhoP(G197A,) PhoP(T199A), and PhoP(R200A)) that specifically affected transcription activation were broadly distributed throughout the transactivation loop extending from Val190 to as far toward the C terminus as Arg200. PhoP(W191A) and PhoP(R200A) could not activate transcription, while the other five mutant proteins showed decreased transcription activation in vivo or in vitro or both. The mutagenesis studies may indicate that PhoP has a long transactivation loop and a short alpha helix 3, more similar to OmpR than to PhoB of Escherichia coli.

  19. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor

    PubMed Central

    Assadi-Porter, Fariba M.; Maillet, Emeline L.; Radek, James T.; Quijada, Jeniffer; Markley, John L.; Max, Marianna

    2010-01-01

    The sweet protein brazzein activates the human sweet receptor, a heterodimeric G-protein coupled receptor (GPCR) composed of subunits T1R2 and T1R3. In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by the in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: Site 1 (Loop43), Site 2 (N- and C-terminus and adjacent Glu36, Loop33), and Site 3 (Loop9–19). Basic residues in Site 1 and acidic residues in Site 2 were essential for positive responses from each assay. Mutation of Y39A (Site 1) greatly reduced positive responses. A bulky side chain at position 54 (Site 2), rather than a side chain with hydrogen bonding potential, was required for positive responses as was the presence of the native disulfide bond in Loop 9–19 (Site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus fly trap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in the brazzein response. The exception, hT1R2:R217A-hT1R3, which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase the positive cooperativity of binding by multiple ligands proposed to bind both T1R subunits (brazzein, monellin, and sucralose) but not those that bind to a single subunit (neotame and cyclamate), we suggest that this site in involved in subunit-subunit interaction rather than direct

  20. Crystal structure of the extended-spectrum β-lactamase PER-2 and insights into the role of specific residues in the interaction with β-lactams and β-lactamase inhibitors.

    PubMed

    Ruggiero, Melina; Kerff, Frédéric; Herman, Raphaël; Sapunaric, Frédéric; Galleni, Moreno; Gutkind, Gabriel; Charlier, Paulette; Sauvage, Eric; Power, Pablo

    2014-10-01

    PER-2 belongs to a small (7 members to date) group of extended-spectrum β-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies toward most β-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 Å and evaluated the possible role of several residues in the structure and activity toward β-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular trans bond between residues 166 to 167, which generates an inverted Ω loop, an expanded fold of this domain that results in a wide active site cavity that allows for efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A β-lactamases. PER β-lactamases might be included within a cluster of evolutionarily related enzymes harboring the conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A ("A" indicates an insertion according to Ambler's scheme for residue numbering in PER β-lactamases), with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different β-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we expect that mutations occurring in these positions will have impacts on the overall hydrolytic behavior.

  1. Crystal Structure of the Extended-Spectrum β-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with β-Lactams and β-Lactamase Inhibitors

    PubMed Central

    Ruggiero, Melina; Kerff, Frédéric; Herman, Raphaël; Sapunaric, Frédéric; Galleni, Moreno; Gutkind, Gabriel; Charlier, Paulette; Sauvage, Eric

    2014-01-01

    PER-2 belongs to a small (7 members to date) group of extended-spectrum β-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies toward most β-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 Å and evaluated the possible role of several residues in the structure and activity toward β-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular trans bond between residues 166 to 167, which generates an inverted Ω loop, an expanded fold of this domain that results in a wide active site cavity that allows for efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A β-lactamases. PER β-lactamases might be included within a cluster of evolutionarily related enzymes harboring the conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A (“A” indicates an insertion according to Ambler's scheme for residue numbering in PER β-lactamases), with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different β-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we expect that mutations occurring in these positions will have impacts on the overall hydrolytic behavior. PMID:25070104

  2. Interactions of the human, rat, Saccharomyces cerevisiae and Escherichia coli 3-methyladenine-DNA glycosylases with DNA containing dIMP residues

    PubMed Central

    Saparbaev, Murat; Mani, Jean-Claude; Laval, Jacques

    2000-01-01

    In DNA, the deamination of dAMP generates 2′-deoxyinosine 5′-monophosphate (dIMP). Hypoxanthine (HX) residues are mutagenic since they give rise to A·T→G·C transition. They are excised, although with different efficiencies, by an activity of the 3-methyladenine (3-meAde)-DNA glycosylases from Escherichia coli (AlkA protein), human cells (ANPG protein), rat cells (APDG protein) and yeast (MAG protein). Comparison of the kinetic constants for the excision of HX residues by the four enzymes shows that the E.coli and yeast enzymes are quite inefficient, whereas for the ANPG and the APDG proteins they repair the HX residues with an efficiency comparable to that of alkylated bases, which are believed to be the primary substrates of these DNA glycosylases. Since the use of various substrates to monitor the activity of HX-DNA glycosylases has generated conflicting results, the efficacy of the four 3-meAde-DNA glycosylases of different origin was compared using three different substrates. Moreover, using oligonucleotides containing a single dIMP residue, we investigated a putative sequence specificity of the enzymes involving the bases next to the HX residue. We found up to 2–5-fold difference in the rates of HX excision between the various sequences of the oligonucleotides studied. When the dIMP residue was placed opposite to each of the four bases, a preferential recognition of dI:T over dI:dG, dI:dC and dI:dA mismatches was observed for both human (ANPG) and E.coli (AlkA) proteins. At variance, the yeast MAG protein removed more efficiently HX from a dI:dG over dI:dC, dI:T and dI:dA mismatches. PMID:10684927

  3. RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...

    EPA Pesticide Factsheets

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.

  4. Conserved Aspartic Acid Residues Lining the Extracellular Loop I of Sodium-coupled Bile Acid Transporter ASBT Interact with Na+ and 7α-OH Moieties on the Ligand Cholestane Skeleton*

    PubMed Central

    Hussainzada, Naissan; Da Silva, Tatiana Claro; Zhang, Eric Y.; Swaan, Peter W.

    2008-01-01

    Functional contributions of residues Val-99—Ser-126 lining extracellular loop (EL) 1 of the apical sodium-dependent bile acid transporter were determined via cysteine-scanning mutagenesis, thiol modification, and in silico interpretation. Despite membrane expression for all but three constructs (S112C, Y117C, S126C), most EL1 mutants (64%) were inactivated by cysteine mutation, suggesting a functional role during sodium/bile acid co-transport. A negative charge at conserved residues Asp-120 and Asp-122 is required for transport function, whereas neutralization of charge at Asp-124 yields a functionally active transporter. D124A exerts low affinity for common bile acids except deoxycholic acid, which uniquely lacks a 7α-hydroxyl (OH) group. Overall, we conclude that (i) Asp-122 functions as a Na+ sensor, binding one of two co-transported Na+ ions, (ii) Asp-124 interacts with 7α-OH groups of bile acids, and (iii) apolar EL1 residues map to hydrophobic ligand pharmacophore features. Based on these data, we propose a comprehensive mechanistic model involving dynamic salt bridge pairs and hydrogen bonding involving multiple residues to describe sodium-dependent bile acid transporter-mediated bile acid and cation translocation. PMID:18508772

  5. Two-body, dry abrasive wear of Fe/Cr/C experimental alloys - relationship between microstructure and mechanical properties

    SciTech Connect

    Kwok, C.K.S.

    1982-01-01

    A systematic study of abrasive wear resistance of Fe/Cr/Mn based alloys has been carried out using a two body pin-on-disc wear machine. Abrasives used were silicon carbide, alumina and quartz. The objective of this study was to evaluate the abrasive wear resistance and to investigate the relationships between microstructure, mechanical properties, and abrasive wear resistance for these experimental alloys. Several commercial alloys were also tested to provide a basis for comparison. The goal of this study was to develop information so as to improve wear resistance of these experimental alloys by means of thermal treatments. Grain-refinement by double heat treatment was carried out in this research.

  6. Exact solution for the metric and the motion of two bodies in (1+1)-dimensional gravity

    NASA Astrophysics Data System (ADS)

    Mann, R. B.; Ohta, T.

    1997-04-01

    We present the exact solution of two-body motion in (1+1)-dimensional dilaton gravity by solving the constraint equations in the canonical formalism. The determining equation of the Hamiltonian is derived in a transcendental form and the Hamiltonian is expressed for the system of two identical particles in terms of the Lambert W function. The W function has two real branches which join smoothly onto each other and the Hamiltonian on the principal branch reduces to the Newtonian limit for a small coupling constant. On the other branch the Hamiltonian yields a new set of motions which cannot be understood as relativistically correcting the Newtonian motion. The explicit trajectory in the phase space (r,p) is illustrated for various values of the energy. The analysis is extended to the case of unequal masses. The full expression of metric tensor is given and the consistency between the solution of the metric and the equations of motion is rigorously proved.

  7. Interaction between γ-radiation and dietary folate starvation metabolically reprograms global hepatic histone H3 methylation at lysine 4 and lysine 27 residues.

    PubMed

    Batra, Vipen; Devasagayam, Thomas Paul Asir

    2012-03-01

    The objective of the present study was to investigate the regulatory control of histone H3 methylation at lysine 4 (H3K4) and lysine 27 (H3K27) residues in response to the effect of folate deficiency and gamma (γ)-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93M formula, were subjected to 2-4 Gy total body γ-irradiation. There was a significant decrease in liver folate levels with concomitant depletion of S-adenosylmethionine (SAM) reserves. Folate deficiency and γ-radiation together induced H3K4 histone methyltransferase (H3K4HMTase) and suppressed H3K27 histone methyltransferase (H3K27HMTase) activities in a dose and time dependent manner. Our studies suggested radiation induced metabolic reprogramming of H3K4/H3K27 methylation patterns in FFD animals. We showed that radiation toxicity diverted one-carbon (C1) flux in FFD fed animals towards H3K4 methylation. Present work on methylation pattern of histone lysine residues gains particular importance as methylation of H3K4 residues is associated with euchromatin while methylated H3K27 residues promote gene silencing. In conclusion, our study suggests that maintenance of genomic histone methylation under γ-radiation stress might be a very dynamic, progressive process that could be modulated by dietary folate deficiency leading to formation of epigenetically reprogrammed cells.

  8. Visual capture and the experience of having two bodies – Evidence from two different virtual reality techniques

    PubMed Central

    Heydrich, Lukas; Dodds, Trevor J.; Aspell, Jane E.; Herbelin, Bruno; Bülthoff, Heinrich H.; Mohler, Betty J.; Blanke, Olaf

    2013-01-01

    In neurology and psychiatry the detailed study of illusory own body perceptions has suggested close links between bodily processing and self-consciousness. One such illusory own body perception is heautoscopy where patients have the sensation of being reduplicated and to exist at two or even more locations. In previous experiments, using a video head-mounted display, self-location and self-identification were manipulated by applying conflicting visuo-tactile information. Yet the experienced singularity of the self was not affected, i.e., participants did not experience having multiple bodies or selves. In two experiments presented in this paper, we investigated self-location and self-identification while participants saw two virtual bodies (video-generated in study 1 and 3D computer generated in study 2) that were stroked either synchronously or asynchronously with their own body. In both experiments, we report that self-identification with two virtual bodies was stronger during synchronous stroking. Furthermore, in the video generated setup with synchronous stroking participants reported a greater feeling of having multiple bodies than in the control conditions. In study 1, but not in study 2, we report that self-location – measured by anterior posterior drift – was significantly shifted towards the two bodies in the synchronous condition only. Self-identification with two bodies, the sensation of having multiple bodies, and the changes in self-location show that the experienced singularity of the self can be studied experimentally. We discuss our data with respect to ownership for supernumerary hands and heautoscopy. We finally compare the effects of the video and 3D computer generated head-mounted display technology and discuss the possible benefits of using either technology to induce changes in illusory self-identification with a virtual body. PMID:24385970

  9. HFOLD - A program package for calculating two-body MSSM Higgs decays at full one-loop level.

    PubMed

    Frisch, W; Eberl, H; Hluchá, H

    2011-10-01

    HFOLD (Higgs Full One Loop Decays) is a Fortran program package for calculating all MSSM Higgs two-body decay widths and the corresponding branching ratios at full one-loop level. The package is done in the SUSY Parameter Analysis convention and supports the SUSY Les Houches Accord input and output format. PROGRAM SUMMARY: Program title: HFOLD Catalogue identifier: AEJG_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJG_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 340 621 No. of bytes in distributed program, including test data, etc.: 1 760 051 Distribution format: tar.gz Programming language: Fortran 77 Computer: Workstation, PC Operating system: Linux RAM: 524 288 000 Bytes Classification: 11.1 External routines: LoopTools 2.2 (http://www.feynarts.de/looptools/), SLHALib 2.2 (http://www.feynarts.de/slha/). The LoopTools code is included in the distribution package. Nature of problem: A future high-energy e+e- linear collider will be the best environment for the precise measurements of masses, cross sections, branching ratios, etc. Experimental accuracies are expected at the per-cent down to the per-mile level. These must be matched from the theoretical side. Therefore higher order calculations are mandatory. Solution method: This program package calculates all MSSM Higgs two-body decay widths and the corresponding branching ratios at full one-loop level. The renormalization is done in the DR scheme following the SUSY Parameter Analysis convention. The program supports the SUSY Les Houches Accord input and output format. Running time: The example provided takes only a few seconds to run.

  10. HFOLD – A program package for calculating two-body MSSM Higgs decays at full one-loop level☆

    PubMed Central

    Frisch, W.; Eberl, H.; Hluchá, H.

    2011-01-01

    HFOLD (Higgs Full One Loop Decays) is a Fortran program package for calculating all MSSM Higgs two-body decay widths and the corresponding branching ratios at full one-loop level. The package is done in the SUSY Parameter Analysis convention and supports the SUSY Les Houches Accord input and output format. Program summary Program title: HFOLD Catalogue identifier: AEJG_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEJG_v1_0.html Program obtainable from: CPC Program Library, Queenʼs University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 340 621 No. of bytes in distributed program, including test data, etc.: 1 760 051 Distribution format: tar.gz Programming language: Fortran 77 Computer: Workstation, PC Operating system: Linux RAM: 524 288 000 Bytes Classification: 11.1 External routines: LoopTools 2.2 (http://www.feynarts.de/looptools/), SLHALib 2.2 (http://www.feynarts.de/slha/). The LoopTools code is included in the distribution package. Nature of problem: A future high-energy e+e− linear collider will be the best environment for the precise measurements of masses, cross sections, branching ratios, etc. Experimental accuracies are expected at the per-cent down to the per-mile level. These must be matched from the theoretical side. Therefore higher order calculations are mandatory. Solution method: This program package calculates all MSSM Higgs two-body decay widths and the corresponding branching ratios at full one-loop level. The renormalization is done in the DR scheme following the SUSY Parameter Analysis convention. The program supports the SUSY Les Houches Accord input and output format. Running time: The example provided takes only a few seconds to run. PMID:21969735

  11. Residual Cap

    NASA Technical Reports Server (NTRS)

    2006-01-01

    10 May 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a summertime view of the south polar residual cap of Mars. In this image, mesas composed largely of solid carbon dioxide are separated from one another by irregularly-shaped depressions. The variation in brightness across this scene is a function of several factors including, but not limited to, varying proportions of dust and solid carbon dioxide, undulating topography, and differences in the roughness of the slopes versus the flat surfaces.

    Location near: 86.7oS, 343.3oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

  12. On tide-induced lagrangian residual current and residual transport: 1. Lagrangian residual current

    USGS Publications Warehouse

    Feng, Shizuo; Cheng, Ralph T.; Pangen, Xi

    1986-01-01

    Residual currents in tidal estuaries and coastal embayments have been recognized as fundamental factors which affect the long-term transport processes. It has been pointed out by previous studies that it is more relevant to use a Lagrangian mean velocity than an Eulerian mean velocity to determine the movements of water masses. Under weakly nonlinear approximation, the parameter k, which is the ratio of the net displacement of a labeled water mass in one tidal cycle to the tidal excursion, is assumed to be small. Solutions for tides, tidal current, and residual current have been considered for two-dimensional, barotropic estuaries and coastal seas. Particular attention has been paid to the distinction between the Lagrangian and Eulerian residual currents. When k is small, the first-order Lagrangian residual is shown to be the sum of the Eulerian residual current and the Stokes drift. The Lagrangian residual drift velocity or the second-order Lagrangian residual current has been shown to be dependent on the phase of tidal current. The Lagrangian drift velocity is induced by nonlinear interactions between tides, tidal currents, and the first-order residual currents, and it takes the form of an ellipse on a hodograph plane. Several examples are given to further demonstrate the unique properties of the Lagrangian residual current.

  13. Two-degree-of-freedom Hamiltonian for the time-symmetric two-body problem of the relativistic action-at-a-distance electrodynamics.

    PubMed

    Buksman Hollander, Efrain; De Luca, Jayme

    2003-02-01

    We find a two-degree-of-freedom Hamiltonian for the time-symmetric problem of straight line motion of two electrons in direct relativistic interaction. This time-symmetric dynamical system appeared 100 years ago and it was popularized in the 1940s by the work of Wheeler and Feynman in electrodynamics, which was left incomplete due to the lack of a Hamiltonian description. The form of our Hamiltonian is such that the action of a Lorentz transformation is explicitly described by a canonical transformation (with rescaling of the evolution parameter). The method is closed and defines the Hamitonian in implicit form without power expansions. We outline the method with an emphasis on the physics of this complex conservative dynamical system. The Hamiltonian orbits are calculated numerically at low energies using a self-consistent steepest-descent method (a stable numerical method that chooses only the nonrunaway solution). The two-degree-of-freedom Hamiltonian suggests a simple prescription for the canonical quantization of the relativistic two-body problem.

  14. Two-degree-of-freedom Hamiltonian for the time-symmetric two-body problem of the relativistic action-at-a-distance electrodynamics

    NASA Astrophysics Data System (ADS)

    Buksman Hollander, Efrain; de Luca, Jayme

    2003-02-01

    We find a two-degree-of-freedom Hamiltonian for the time-symmetric problem of straight line motion of two electrons in direct relativistic interaction. This time-symmetric dynamical system appeared 100 years ago and it was popularized in the 1940s by the work of Wheeler and Feynman in electrodynamics, which was left incomplete due to the lack of a Hamiltonian description. The form of our Hamiltonian is such that the action of a Lorentz transformation is explicitly described by a canonical transformation (with rescaling of the evolution parameter). The method is closed and defines the Hamitonian in implicit form without power expansions. We outline the method with an emphasis on the physics of this complex conservative dynamical system. The Hamiltonian orbits are calculated numerically at low energies using a self-consistent steepest-descent method (a stable numerical method that chooses only the nonrunaway solution). The two-degree-of-freedom Hamiltonian suggests a simple prescription for the canonical quantization of the relativistic two-body problem.

  15. Identification of hormone-interacting amino acid residues within the steroid-binding domain of the glucocorticoid receptor in relation to other steroid hormone receptors

    SciTech Connect

    Carlstedt-Duke, J.; Stroemstedt, P.E.; Persson, B.; Cederlund, E.; Gustafsson, J.A.; Joernvall, H.

    1988-05-15

    Purified rat liver glucocorticoid receptor was covalently charged with (/sup 3/H)glucocorticoid by photoaffinity labeling (UV irradiation of (/sup 3/H)triamcinolone acetonide-glucocorticoid receptor) or affinity labeling (incubation with (/sup 3/H)dexamethasone mesylate). After labeling, separate samples of the denatured receptor were cleaved with trypsin (directly or after prior succinylation), chymotrypsin, and cyanogen bromide. Labeled residues in the peptides obtained were identified by radiosequence analysis. The peaks of radioactivity corresponded to Met-622 and Cys-754 after photoaffinity labeling with (/sup 3/H)triamcinolone acetonide and Cys-656 after affinity labeling with (/sup 3/H)dexamethasone mesylate. The labeled residues are all positioned within hydrophobic segments of the steroid-binding domain. The patterns of hydropathy and secondary structure for the glucocorticoid receptor are highly similar to those for the progestin receptor and similar but less so to those for the estrogen receptor and to those for c-erb A.

  16. Thermochemical pretreatment of lignocellulose residues: assessment of the effect on operational conditions and their interactions on the characteristics of leachable fraction.

    PubMed

    Vásquez, Denisse; Contreras, Elsa; Palma, Carolyn; Carvajal, Andrea

    2015-01-01

    Annually, large amounts of agricultural residues are produced in Chile, which can be turned into a good opportunity to diversify the energy matrix. These residues have a slow hydrolysis stage during anaerobic digestion; therefore, the application of a pretreatment seems to be an alternative to improve the process. This work focused on applying a thermochemical pretreatment with NaOH on two lignocellulosic residues. The experiments were performed according to a 2(4) factorial design. The factors studied in a 2(4) factorial design were: temperature (60 and 120 °C), pretreatment time (10 and 30 minutes), NaOH dose (2 and 4%), and residue size (<1 and 1-3 mm for wheat straw; 1-5 and 5-10 mm for corn stover). The analyzed response variables were the solubilization of organic matter, and the biodegradability of the lignocellulose hydrolysate. The statistical analysis of the data allowed the identification of the experimental conditions that maximized solubilization of organic matter and biodegradability. The main results showed that more aggressive experimental conditions could increase the breaking down of the structure; in addition, the time of pretreatment was not significant. Conversely, the less aggressive experimental conditions, regarding regent dosage and downsizing, favored the release of biodegradable organic matter. The main conclusion of this study was the identification of the operational conditions of the thermochemical pretreatment that promote maximum biogas production, which was caused due to the solubilization of a large amount of organic matter, but not because of the increase in biodegradability of the released organic matter.

  17. Residues of the human nuclear vitamin D receptor that form hydrogen bonding interactions with the three hydroxyl groups of 1alpha,25-dihydroxyvitamin D3.

    PubMed

    Reddy, Madhuri D; Stoynova, Ludmilla; Acevedo, Alejandra; Collins, Elaine D

    2007-03-01

    Most of the biological effects of 1,25-dihydroxyvitamin D(3) (hormone D) are mediated through the nuclear vitamin D receptor (VDR). Hormone binding induces conformational changes in VDR that enable the receptor to activate gene transcription. It is known that residues S237 and R274 form hydrogen bonds with the 1-hydroxyl group of hormone D, while residues Y143 and S278, and residues H305 and H397 form hydrogen bonds with the 3-hydroxyl and the 25-hydroxyl groups of the hormone. A series of VDR mutations were constructed (S237A, R274A, R274Q, Y143F, Y143A, S278A, H305A, and H397F; double mutants: S237A/R274A, Y143F/S278A, Y143A/S278A, and H305A/H397F). The relative binding affinities of the wild-type and variant VDRs were assessed. All of the mutants except H397F resulted in lower binding affinity compared to wild-type VDR. Binding to hormone was barely detectable in Y143F, H305A, and H305A/H397F mutants, and undetectable in mutants R274A, R274Q, Y143A, S237A/R274A, and Y143A/S278A, indicating the importance of these residues. Ability to activate gene transcription was also assessed. All of the VDR mutants, except the single mutant S278A, required higher doses of hormone D for half-maximal response. Defining the role of hormone D-VDR binding will lead to a better understanding of the vitamin D signal transduction pathway.

  18. Interaction of 5'-P-sulfonylbenzoyl adenosine with cysteine residues of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase

    SciTech Connect

    El-Maghrabi, M.R.; Lively, M.O.; Pilkis, S.J.

    1987-05-01

    The kinase and bisphosphatase reactions of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase appear to be catalyzed at separate active sites. The kinase site contains 3 cysteinyl residues that are important for sugar phosphate binding but not for ATP binding. These groups are readily alkylated with iodoacetamide which decreases by 15-fold the affinity for Fru 6-P but also increases the maximal velocity of the reaction by the same extent. Incubation of the enzyme with 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), an ATP analog, has no effect on the bisphosphatase activity but inactivates the kinase. The addition of dithiothreitol completely reactivates the kinase, suggesting that the reagent affected sulfhydryl groups critical for sugar phosphate binding and not the ATP site of the enzyme. Similarly, 8-Azido-ATP/UV-photoinactivated enzyme is also reactivated by dithiothreitol and involves the same sulfhydryl groups, since alkylation of the latter with iodoacetamide protects the enzyme from inactivation by FSBA and from 8-azido ATP. Cyanogen bromide cleavage of enzyme that had been alkylated with iodo(I-/sup 14/C)acetamide yielded a 20,000 dalton peptide which contained the three cysteinyl residues. It is concluded that the site of action of ATP analogs to inactivate the kinase are these cysteinyl residues rather than the ATP binding site per se.

  19. Precompound emission in low-energy heavy-ion interactions from recoil range and spin distributions of heavy residues: A new experimental method

    NASA Astrophysics Data System (ADS)

    Sharma, Manoj Kumar; Singh, Pushpendra P.; Sharma, Vijay Raj; Shuaib, Mohd.; Singh, Devendra P.; Yadav, Abhishek; Unnati, Kumar, R.; Singh, B. P.; Prasad, R.

    2016-10-01

    Recent investigations of heavy-ion reactions at low incident energies have indicated the presence of precompound emission component in considerable strength. In most cases the strength of the precompound component is estimated from the difference in forward-backward distributions of emitted light fast particles and also from the analysis of the measured excitation functions. This paper reports a new method of deciphering the relative contributions of compound and precompound components associated with fusion of 16O with 159Tb,169Tm, and 181Ta targets by measuring the recoil ranges of heavy residues in an absorbing medium along with the online measurement of the spin distributions in reaction residues produced in the fusion 16O beam with 159Tb and 169Tm targets. Analysis of recoil range and spin distributions of the residues shows two distinct linear momentum-transfer components corresponding to precompound and compound nucleus processes. The input angular momentum associated with precompound products is found to be relatively lower than that associated with compound nucleus process. The precompound components obtained from the present analysis are consistent with those obtained from the analysis of excitation functions.

  20. Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.

    PubMed

    Naqsh e Zahra, Syeda; Khattak, Naureen Aslam; Mir, Asif

    2013-01-01

    Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely

  1. Computational Prediction of Hot Spot Residues

    PubMed Central

    Morrow, John Kenneth; Zhang, Shuxing

    2013-01-01

    Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein-protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues. PMID:22316154

  2. Classical density functional theory and the phase-field crystal method using a rational function to describe the two-body direct correlation function.

    PubMed

    Pisutha-Arnond, N; Chan, V W L; Iyer, M; Gavini, V; Thornton, K

    2013-01-01

    We introduce a new approach to represent a two-body direct correlation function (DCF) in order to alleviate the computational demand of classical density functional theory (CDFT) and enhance the predictive capability of the phase-field crystal (PFC) method. The approach utilizes a rational function fit (RFF) to approximate the two-body DCF in Fourier space. We use the RFF to show that short-wavelength contributions of the two-body DCF play an important role in determining the thermodynamic properties of materials. We further show that using the RFF to empirically parametrize the two-body DCF allows us to obtain the thermodynamic properties of solids and liquids that agree with the results of CDFT simulations with the full two-body DCF without incurring significant computational costs. In addition, the RFF can also be used to improve the representation of the two-body DCF in the PFC method. Last, the RFF allows for a real-space reformulation of the CDFT and PFC method, which enables descriptions of nonperiodic systems and the use of nonuniform and adaptive grids.

  3. Local NH-π interactions involving aromatic residues of proteins: influence of backbone conformation and ππ* excitation on the π H-bond strength, as revealed from studies of isolated model peptides.

    PubMed

    Sohn, Woon Yong; Brenner, Valérie; Gloaguen, Eric; Mons, Michel

    2016-11-02

    Conformer-selective IR gas phase spectroscopy and high level quantum chemistry methods have been used to characterise the diversity of local NH-π interactions between the π ring of a phenylalanine aromatic residue and the nearby main chain amide groups. The study of model systems shows how the amide NH stretch vibrational features, in the 3410-3460 cm(-1) frequency range, can be used to monitor the strength of these local π H-bonds, which is found to depend on both the backbone conformation and the aromatic side chain orientation. This is rationalized in terms of partial electron transfer between the π cloud and the main chain NH bonds, with the help of analysis tools based on Natural Bonding Orbitals and Non-Covalent Interactions plots. The experimental study, extended to the NH-π interactions when the Phe residue is excited in its first ππ* electronic state, also demonstrates the principle of the ππ* labelling technique, i.e. a selective labelling of those NH bonds in a peptide molecule that are in close contact with an aromatic ring, as an elegant tool for IR spectroscopic assignments. The validation of theoretical predictions against experimental data (frequency change upon excitation) eventually qualifies the use of the CC2 method for the description of the ππ* excited states of systems having a phenyl ring, both in terms of structure, vibrational modes and nature of excited states.

  4. Dental materials for primary dentition: are they suitable for occlusal restorations? A two-body wear study.

    PubMed

    Lazaridou, D; Belli, R; Krämer, N; Petschelt, A; Lohbauer, U

    2015-04-01

    This was to evaluate the wear resistance of different materials, compomers, resin-modified glass ionomer cements (RMGICs), glass ionomer cements (GICs), used for posterior restorations in primary teeth and to compare the results with the reference material, amalgam. Eight specimens of each material were subjected to two-body wear test, using a chewing simulator. The wear region of each material was examined under a profilometer, measuring the vertical loss (μm) and the volume loss (mm(3)) of the materials. The results showed significant differences of vertical loss and volume loss of the test materials (p < 0.001). Amalgam had the highest wear resistance. Twinky Star (compomer) had the lowest vertical loss and volume loss. There was no significant difference of vertical loss among compomers, Dyract Extra, Dyract Flow and Dyract Posterior. Riva Self Cure (GIC) had no statistically significant difference compared with the compomers (except Twinky Star). No statistically significant difference was found also between Equia (GIC) and Ketac Moral (GIC) with Dyract Extra (Compomer). RMGICs were found to have the lowest wear resistance. For the statistical analysis, the PASW 20.0 (SPSS Statistics, IBM, Chicago) package was used. Means and standard deviations were measured with descriptive statistics and analyzed using one-way ANOVA. Compomers and some GICs, that have moderate wear resistance, may be sufficient for occlusal restorations in primary dentitions.

  5. Measurement of Branching Fractions for Two-Body Charmless B Decays to Charged Pions and Kaons at BaBar

    SciTech Connect

    Barrera, Barbara

    2000-08-28

    The authors present preliminary results of a search for charmless two-body B decays to charged pions and kaons using data collected by the BaBar detector at the Stanford Linear Accelerator Center's PEP-II Storage ring. In a sample of 8.8 million produced B anti-B pairs the authors measure the branching fractions beta(B{sup 0} --> pi{sup +}pi{sup {minus}}) = (9.3{sub {minus}2.3{minus}1.4}{sup +2.6+1.2}) x 10{sup {minus}6} and beta(B{sup 0} --> K{sup +}pi{sup {minus}}) = (12.5{sub {minus}2.6{minus}1.7}{sup +3.0+1.3}) x 10{sup {minus}6}, where the first uncertainty is statistical and the second is systematic. For the decay B{sup 0} --> K{sup +}K{sup {minus}} they find no significant signal and set an upper limit of beta(B{sup 0} --> K{sup +}K{sup {minus}}) < 6.6 x 10{sup {minus}6} at the 90% confidence level.

  6. Two-body decays of gluino at full one-loop level in the quark-flavour violating MSSM.

    PubMed

    Eberl, Helmut; Ginina, Elena; Hidaka, Keisho

    2017-01-01

    We study the two-body decays of the gluino at full one-loop level in the Minimal Supersymmetric Standard Model with quark-flavour violation (QFV) in the squark sector. The renormalisation is done in the [Formula: see text] scheme. The gluon and photon radiations are included by adding the corresponding three-body decay widths. We discuss the dependence of the gluino decay widths on the QFV parameters. The main dependence stems from the [Formula: see text]-[Formula: see text] mixing in the decays to up-type squarks, and from the [Formula: see text]-[Formula: see text] mixing in the decays to down-type squarks due to the strong constraints from B-physics on the other quark-flavour-mixing parameters. The full one-loop corrections to the gluino decay widths are mostly negative and of the order of about -10%. The QFV part stays small in the total width but can vary up to -8% for the decay width into the lightest [Formula: see text] squark. For the corresponding branching ratio the effect is somehow washed out by at least a factor of two. The electroweak corrections can be as large as 35% of the SUSY QCD corrections.

  7. Global analysis of two-body D →V P decays within the framework of flavor symmetry

    NASA Astrophysics Data System (ADS)

    Cheng, Hai-Yang; Chiang, Cheng-Wei; Kuo, An-Li

    2016-06-01

    Two-body charmed meson decays D →V P are studied within the framework of the diagrammatic approach. Under flavor SU(3) symmetry, all the flavor amplitude sizes and their associated strong phases are extracted by performing a χ2 fit. Thanks to the recent measurement of Ds+→π+ρ0 , the magnitudes and the strong phases of the W -annihilation amplitudes AP ,V have been extracted for the first time. As a consequence, the branching fractions of all the D →V P decays are predicted, especially those modes that could not be predicted previously due to the unknown AP ,V. Our working assumption, the flavor SU(3) symmetry, is tested by comparing our predictions with experiment for the singly and doubly Cabibbo-suppressed decay modes based on the flavor amplitudes extracted from the Cabibbo-favored decays using the current data. The predictions for the doubly Cabibbo-suppressed channels are in good agreement with the data, while those for the singly Cabibbo-suppressed decay modes are seen to have flavor SU(3) symmetry breaking effects. We find that the inclusion of SU(3) symmetry breaking in color-allowed and color-suppressed tree amplitudes is needed in general in order to have a better agreement with experiment. Nevertheless, the exact flavor SU(3)-symmetric approach alone is adequate to provide an overall explanation for the current data.

  8. Analysis of two-body charmed B meson decays in factorization-assisted topological-amplitude approach

    NASA Astrophysics Data System (ADS)

    Zhou, Si-Hong; Wei, Yan-Bing; Qin, Qin; Li, Ying; Yu, Fu-Sheng; Lü, Cai-Dian

    2015-11-01

    Within the factorization-assisted topological-amplitude approach, we study the two-body charmed B meson decays Bu ,d ,s→D(*)M , with M denoting a light pseudoscalar (or vector) meson. The meson decay constants and transition form factors are factorized out from the hadronic matrix element of topological diagrams. Therefore, the effect of SU(3) symmetry breaking is retained, which is different from the conventional topological diagram approach. The number of free nonperturbative parameters to be fitted from experimental data is also much less. Only four universal nonperturbative parameters χC, ϕC, χE and ϕE are introduced to describe the contribution of the color-suppressed tree and W -exchanged diagrams for all the decay channels. With the fitted parameters from 31 decay modes induced by b →c transition, we then predict the branching fractions of 120 decay modes induced by both b →c and b →u transitions. Our results are well consistent with the measured data or to be tested in the LHCb and Belle-II experiments in the future. Besides, the SU(3) symmetry breaking, isospin violation and C P asymmetry are also investigated.

  9. Intermolecular 'cross-torque': the N4-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction.

    PubMed

    Domingo, Olwen; Hellmuth, Isabell; Jäschke, Andres; Kreutz, Christoph; Helm, Mark

    2015-06-23

    Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson-Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson-Crick face of N(4)-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N(4)-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the 'CH'-edge as a result of base pairing on the Watson-Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson-Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the 'CH'-edge, consequently preventing Watson-Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N(4)-substituents to make way for Watson-Crick base pairing, providing no steric hindrance is present on the 'CH'-edge.

  10. Intermolecular ‘cross-torque’: the N4-cytosine propargyl residue is rotated to the ‘CH’-edge as a result of Watson–Crick interaction

    PubMed Central

    Domingo, Olwen; Hellmuth, Isabell; Jäschke, Andres; Kreutz, Christoph; Helm, Mark

    2015-01-01

    Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson–Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson–Crick face of N4-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N4-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the ‘CH’-edge as a result of base pairing on the Watson–Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson–Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the ‘CH’-edge, consequently preventing Watson–Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N4-substituents to make way for Watson–Crick base pairing, providing no steric hindrance is present on the ‘CH’-edge. PMID:25934805

  11. Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction.

    PubMed

    Lin, Han-Xin; Feng, Yan; Wong, Gillian; Wang, Liping; Li, Bei; Zhao, Xuesen; Li, Yan; Smaill, Fiona; Zhang, Chengsheng

    2008-04-01

    Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. Like severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the human angiotensin-converting enzyme 2 (hACE2) receptor for cellular entry. To identify residues in the spike protein of NL63 that are important for hACE2 binding, this study first generated a series of S1-truncated variants, examined their associations with the hACE2 receptor and subsequently mapped a minimal receptor-binding domain (RBD) that consisted of 141 residues (aa 476-616) towards the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD bound to hACE2 more efficiently than its full-length counterpart and had a binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of RBD variants was generated using site-directed mutagenesis and random mutant library screening assays, and identified 15 residues (C497, Y498, V499, C500, K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that appeared to be critical for the RBD-hACE2 association. These critical residues clustered in three separate regions (designated RI, RII and RIII) inside the RBD, which may represent three receptor-binding sites. These results may help to delineate the molecular interactions between the S protein of NL63 and the hACE2 receptor, and may also enhance our understanding of the pathogenesis of NL63 and SARS-CoV.

  12. Two-Body Orbit Expansion Due to Time-Dependent Relative Acceleration Rate of the Cosmological Scale Factor

    NASA Astrophysics Data System (ADS)

    Iorio, Lorenzo

    2014-01-01

    By phenomenologically assuming a slow temporal variation of the percent acceleration rate S̈S -1 of the cosmic scale factor S(t), it is shown that the orbit of a local binary undergoes a secular expansion. To first order in the power expansion of S̈S -1 around the present epoch t0, a non-vanishing shift per orbit (Δr) of the two-body relative distance r occurs for eccentric trajectories. A general relativistic expression, which turns out to be cubic in the Hubble parameter H0 at the present epoch, is explicitly calculated for it in the case of matter-dominated epochs with Dark Energy. For a highly eccentric Oort comet orbit with period Pb ≈ 31 Myr, the general relativistic distance shift per orbit turns out to be of the order of (Δr) ≈ 70 km. For the Large Magellanic Cloud, assumed on a bound elliptic orbit around the Milky Way, the shift per orbit is of the order of (Δr) ≈ 2-4 pc. Our result has a general validity since it holds in any cosmological model admitting the Hubble law and a slowly varying S̈S-1(t). More generally, it is valid for an arbitrary Hooke-like extra-acceleration whose "elastic" parameter κ is slowly time-dependent, irrespectively of the physical mechanism which may lead to it. The coefficient κ1 of the first-order term of the power expansion of κ(t) can be preliminarily constrained in a model-independent way down to a κ1 ≤ 2 x 10-13 year-3 level from latest Solar System's planetary observations. The radial velocities of the double lined spectroscopic binary ALPHA Cen AB yield κ1 ≤ 10-8 year-3.

  13. Charmless two-body B{sub (s)}{yields}VP decays in soft collinear effective theory

    SciTech Connect

    Wang Wei; Wang Yuming; Yang Deshan; Lue Caidian

    2008-08-01

    We provide the analysis of charmless two-body B{yields}VP decays under the framework of the soft collinear effective theory (SCET), where V(P) denotes a light vector (pseudoscalar) meson. Besides the leading power contributions, some power corrections (chiraly enhanced penguins) are also taken into account. Using the current available B{yields}PP and B{yields}VP experimental data on branching fractions and CP asymmetry variables, we find two kinds of solutions in {chi}{sup 2} fit for the 16 nonperturbative inputs which are essential in the 87 B{yields}PP and B{yields}VP decay channels. Chiraly enhanced penguins can change several charming penguins sizably, since they share the same topology. However, most of the other nonperturbative inputs and predictions on branching ratios and CP asymmetries are not changed too much. With the two sets of inputs, we predict the branching fractions and CP asymmetries of other modes especially B{sub s}{yields}VP decays. The agreements and differences with results in QCD factorization and perturbative QCD approach are analyzed. We also study the time-dependent CP asymmetries in channels with CP eigenstates in the final states and some other channels such as B{sup 0}/B{sup 0}{yields}{pi}{sup {+-}}{rho}{sup {+-}} and B{sub s}{sup 0}/B{sub s}{sup 0}{yields}K{sup {+-}}K*{sup {+-}}. In the perturbative QCD approach, the (S-P)(S+P) penguins in annihilation diagrams play an important role. Although they have the same topology with charming penguins in SCET, there are many differences between the two objects in weak phases, magnitudes, strong phases, and factorization properties.

  14. Two-Body Photodisintegration of ^3He between 0.4 and 1.5 GeV

    NASA Astrophysics Data System (ADS)

    Ilieva, Yordanka

    2006-04-01

    The γ^3He->pd reaction was measured with the CLAS detector at Jefferson Lab for photon energies between 0.4 and 1.5 GeV and proton CM angles p̂CM between 40^o and 140^o. It is complementary to the three-body breakup of ^3He with respect to studying three-body mechanisms. At all photon energies for our experiment, the differential cross sections exhibit a very strong forward-to-backward asymmetry --- approximately one order of magnitude. An interesting feature of the differential cross sections is that their slope does not depend on the photon energy and there is a change of slope at p̂CM=120^o seen at all photon energies. The invariant cross sections fall off with s (where s is the total CM energy) much faster than expected by the quark counting rules [1]. The latter predict that in the asymptotic regime t->∞ the invariant cross sections should scale as s-17, whereas our data scale as s-22. A comparison of our preliminary results with the cross sections predicted by Jean-Marc Laget's model [2] shows that the differential cross sections for angles greater than 60^o are sensitive to contributions from three-body mechanisms. The relative importance of the latter, with respect to one- and two-body mechanisms, is larger at 0.6 - 0.8 GeV than at higher energies. This has already been observed in our data for γ^3He->ppn [3] and seems to be a characteristic of the three-body mechanisms at medium energies. 6mm 1. S.J. Brodsky and G.R. Farrar, Phys. Rev. Lett. 31, 1153 (1973) 2. J-M. Laget, Phys. Rev. C 38, 2993 (1988)3. S. Niccolai et al., Phys. Rev. C 70, 064003 (2004)

  15. A cluster of aspartic residues in the extracellular loop II of PAR 4 is important for thrombin interaction and activation of platelets.

    PubMed

    Sánchez Centellas, Daniel; Gudlur, Sushanth; Vicente-Carrillo, Alejandro; Ramström, Sofia; Lindahl, Tomas L

    2017-06-01

    Thrombin activates platelets via proteolytic cleavage of protease-activated receptors (PARs) 1 and 4. The two PARs have distinct but complementary roles. The mechanisms responsible for PAR1 activation by thrombin have been extensively studied. However, much less is known regarding thrombin activation of PAR4, especially the potential involvement of regions of PAR4 other than the N-terminal, which is bound to the catalytic site of thrombin. We have studied PAR4 in S. cerevisiae strain MMY12, an expression system in which the GPCR receptors are connected to a Lac Z reporter gene resulting in increased β-galactosidase activity. This approach was used to assess PAR4 mutants to evaluate the contribution of different aspartic residues in facilitating PAR4 activation. Furthermore, peptides mimicking parts of the PAR4 N-terminal and the second extracellular loop (ECLII) were tested for their ability to inhibit platelet activation by thrombin. Binding of these peptides to γ-thrombin was studied by monitoring the decrease in tryptophan fluorescence intensity of thrombin. We conclude that not only the N-terminal but also the electronegative aspartic residues D224, D230 and D235 (located in ECLII) are be important for PAR4 binding to thrombin. We further suggest that they play a role for the tethered ligand binding to the receptor, as mutations also affected activation in response to a PAR4-activating peptide mimicking the new N-terminal formed after cleavage. This agrees with previous results on PAR1 and thrombin binding. We suggest that the ECLII of PAR4 could be a potential target for antithrombotic drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Spring Chinook Salmon Interactions Indices and Residual/Precocious Male Monitoring in the Upper Yakima Basin; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2004-2005 Annual Report.

    SciTech Connect

    Pearsons, Todd N.; Johnson, Christopher L.; James, Brenda B.

    2005-05-01

    This report examines some of the factors that can influence the success of supplementation, which is currently being tested in the Yakima Basin using upper Yakima stock of spring chinook salmon. Supplementation success in the Yakima Basin is defined relative to four topic areas: natural production, genetics, ecological interactions, and harvest (Busack et al. 1997). The success of spring chinook salmon supplementation in the Yakima Basin is dependent, in part, upon fish culture practices and favorable physical and biological conditions in the natural environment (Busack et al. 1997; James et al. 1999; Pearsons et al., 2003; Pearsons et al. 2004). Shortfalls in either of these two topics (i.e., failure in culturing many fish that have high long-term fitness or environmental conditions that constrain spring chinook salmon production) will cause supplementation success to be limited. For example, inadvertent selection or propagation of spring chinook that residualize or precocially mature may hinder supplementation success. Spring chinook salmon that residualize (do not migrate during the normal migration period) may have lower survival rates than migrants and, additionally, may interact with wild fish and cause unacceptable impacts to non-target taxa. Large numbers of precocials (nonanadromous spawners) may increase competition for females and significantly skew ratios of offspring sired by nonanadromous males, which could result in more nonanadromous spring chinook in future generations. Conditions in the natural environment may also limit the success of spring chinook supplementation. For example, intra or interspecific competition may constrain spring chinook salmon production. Spring chinook salmon juveniles may compete with each other for food or space or compete with other species that have similar ecological requirements. Monitoring of spring chinook salmon residuals, precocials, prey abundance, carrying capacity, and competition will help researchers

  17. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins.

    PubMed

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, C T; Surjit, Milan

    2016-04-26

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66(th),67(th) isoleucine and 101(st),102(nd) leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV.

  18. Identification of critical residues in Hepatitis E virus macro domain involved in its interaction with viral methyltransferase and ORF3 proteins

    PubMed Central

    Anang, Saumya; Subramani, Chandru; Nair, Vidya P.; Kaul, Sheetal; Kaushik, Nidhi; Sharma, Chandresh; Tiwari, Ashutosh; Ranjith-Kumar, CT; Surjit, Milan

    2016-01-01

    Hepatitis E virus (HEV) is a major cause of hepatitis in normal and organ transplant individuals. HEV open reading frame-1 encodes a polypeptide comprising of the viral nonstructural proteins as well as domains of unknown function such as the macro domain (X-domain), V, DUF3729 and Y. The macro domain proteins are ubiquitously present from prokaryotes to human and in many positive-strand RNA viruses, playing important roles in multiple cellular processes. Towards understanding the function of the HEV macro domain, we characterized its interaction partners among other HEV encoded proteins. Here, we report that the HEV X-domain directly interacts with the viral methyltransferase and the ORF3 proteins. ORF3 association with the X-domain was mediated through two independent motifs, located within its N-terminal 35aa (amino acids) and C-terminal 63-123aa. Methyltransferase interaction domain was mapped to N-terminal 30-90aa. The X-domain interacted with both ORF3 and methyltransferase through its C-terminal region, involving 66th,67th isoleucine and 101st,102nd leucine, conserved across HEV genotypes. Furthermore, ORF3 and methyltransferase competed with each other for associating with the X-domain. These findings provide molecular understanding of the interaction between the HEV macro domain, methyltransferase and ORF3, suggesting an important role of the macro domain in the life cycle of HEV. PMID:27113483

  19. Identification of specific amino acid residues in the E. coli beta processivity clamp involved in interactions with DNA polymerase III, UmuD and UmuD'.

    PubMed

    Duzen, Jill M; Walker, Graham C; Sutton, Mark D

    2004-03-04

    Variants of a pentapeptide sequence (QL[S/F]LF), referred to as the eubacterial clamp-binding motif, appear to be required for certain proteins to bind specifically to the Escherichia coli beta sliding clamp, apparently by making contact with a hydrophobic pocket located at the base of the C-terminal tail of each beta protomer. Although both UmuC (DNA pol V) and the alpha catalytic subunit of DNA polymerase III (pol III) each bear a reasonable match to this motif, which appears to be required for their respective interactions with the clamp, neither UmuD not UmuD' do. As part of an ongoing effort to understand how interactions involving the different E. coli umuDC gene products and components of DNA polymerase III help to coordinate DNA replication with a DNA damage checkpoint control and translesion DNA synthesis (TLS) following DNA damage, we characterized the surfaces on beta important for its interactions with the two forms of the umuD gene product. We also characterized the surface of beta important for its interaction with the alpha catalytic subunit of pol III. Our results indicate that although UmuD, UmuD' and alpha share some common contacts with beta, each also makes unique contacts with the clamp. These findings suggest that differential interactions of UmuD and UmuD' with beta impose a DNA damage-responsive conditionality on how beta interacts with the translesion DNA polymerase UmuC. This is formally analogous to how post-translational modification of the eukaryotic PCNA clamp influences mutagenesis. We discuss the implications of our findings in terms of how E. coli might coordinate the actions of the umuDC gene products with those of pol III, as well as for how organisms in general might manage the actions of their multiple DNA polymerases. Copyright 2003 Elsevier B.V.

  20. Functional Characterization of the re-Face Loop Spanning Residues 536 to 541 and its Interactions with the Cofactor in the Flavin Mononucleotide-Binding Domain of the Flavocytochrome P450 from Bacillus megaterium†

    PubMed Central

    Kasim, Mumtaz; Chen, Huai-Chun; Swenson, Richard P.

    2009-01-01

    Flavocytochrome P450BM-3, a bacterial monooxygenase, contains a flavin mononucleotide (FMN) binding domain bearing a strong structural homology to the bacterial flavodoxin. The FMN serves as the one-electron donor to the heme iron but, in contrast to the electron transfer mechanism of mammalian cytochrome P450 reductase, the FMN semiquinone state is not thermodynamically stable and appears transiently as the anionic rather than the neutral form. A unique loop region comprised of residues -536Y-N-G-H-P-P541-, which forms a Type I′ reverse turn, provides several interactions with the FMN isoalloxazine ring, was targeted in this study. Nuclear magnetic resonance studies support the presence of a strong hydrogen bond between the backbone amide of Asn537 and FMN N5, the anionic ionization state of the hydroquinone, and for a change in the hybridization state of the N5 upon reduction. Replacement of Tyr536, which flanks the flavin ring, by the basic residues histidine or arginine did not significantly influence the redox properties of the FMN or the accumulation of the anionic semiquinone. The central residues of the Type I′ turn (-Asn-Gly-) were replaced with various combinations of glycine and alanine as a means to alter the turn and its interactions. Gly538 was found to be crucial in maintaining the type I′ turn conformation of the loop and the strong H-bonding interaction at N5. The functional role of the tandem –Pro-Pro- sequence which anchors and possible “rigidifies” the loop was investigated through alanine replacements. Despite changes in stabilities of the oxidized and hydroquinone redox states of the FMN, none of the replacements studied significantly altered the two-electron midpoint potentials. Pro541 does contribute to some degree to the strength of the N5 interaction, the formation of the anionic semiquinone. Unlike the flavodoxin, it would appear that the conformation of the FMN rather than the loop changes in response to reduction in this

  1. Turbulence Fine Structure, Intermittency, and Large-Scale Interactions in the Stable Boundary Layer and Residual Layer: Correlative High-Resolution Measurements and Direct Numerical Simulations

    DTIC Science & Technology

    2014-12-06

    arise from, and drive, successive instabilities including Kelvin-Helmholtz instabilities (KHI), gravity wave breaking (GWB), and more general fluid...Research Triangle Park, NC 27709-2211 stable boundary layer, multi-scale interactions, Kelvin-Helmholtz instabilities, gravity wave breaking, turbulence...arise from, and drive, successive instabilities including Kelvin-Helmholtz instabilities (KHI), gravity wave breaking (GWB), and more general fluid

  2. Modeling Latent Interactions at Level 2 in Multilevel Structural Equation Models: An Evaluation of Mean-Centered and Residual-Centered Unconstrained Approaches

    ERIC Educational Resources Information Center

    Leite, Walter L.; Zuo, Youzhen

    2011-01-01

    Among the many methods currently available for estimating latent variable interactions, the unconstrained approach is attractive to applied researchers because of its relatively easy implementation with any structural equation modeling (SEM) software. Using a Monte Carlo simulation study, we extended and evaluated the unconstrained approach to…

  3. Modeling Latent Interactions at Level 2 in Multilevel Structural Equation Models: An Evaluation of Mean-Centered and Residual-Centered Unconstrained Approaches

    ERIC Educational Resources Information Center

    Leite, Walter L.; Zuo, Youzhen

    2011-01-01

    Among the many methods currently available for estimating latent variable interactions, the unconstrained approach is attractive to applied researchers because of its relatively easy implementation with any structural equation modeling (SEM) software. Using a Monte Carlo simulation study, we extended and evaluated the unconstrained approach to…

  4. The TDF System for Thermonuclear Plasma Reaction Rates, Mean Energies and Two-Body Final State Particle Spectra

    SciTech Connect

    Warshaw, S I

    2001-07-11

    The rate of thermonuclear reactions in hot plasmas as a function of local plasma temperature determines the way in which thermonuclear ignition and burning proceeds in the plasma. The conventional model approach to calculating these rates is to assume that the reacting nuclei in the plasma are in Maxwellian equilibrium at some well-defined plasma temperature, over which the statistical average of the reaction rate quantity {sigma}v is calculated, where {sigma} is the cross-section for the reaction to proceed at the relative velocity v between the reacting particles. This approach is well-understood and is the basis for much nuclear fusion and astrophysical nuclear reaction rate data. The Thermonuclear Data File (TDF) system developed at the Lawrence Livermore National Laboratory (Warshaw 1991), which is the topic of this report, contains data on the Maxwellian-averaged thermonuclear reaction rates for various light nuclear reactions and the correspondingly Maxwellian-averaged energy spectra of the particles in the final state of those reactions as well. This spectral information closely models the output particle and energy distributions in a burning plasma, and therefore leads to more accurate computational treatments of thermonuclear burn, output particle energy deposition and diagnostics, in various contexts. In this report we review and derive the theoretical basis for calculating Maxwellian-averaged thermonuclear reaction rates, mean particle e