Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity

In this work, two different docking programs were used, AutoDock and FlexX, which use different types of scoring functions and searching methods. The docking poses of all quinone compounds studied stayed in the same region in the trypanothione reductase. This region is a hydrophobic pocket near to Phe396, Pro398 and Leu399 amino acid residues. The compounds studied displays a higher affinity in trypanothione reductase (TR) than glutathione reductase (GR), since only two out of 28 quinone compounds presented more favorable docking energy in the site of human enzyme. The interaction of quinone compounds with the TR enzyme is in agreement with other studies, which showed different binding sites from the ones formed by cysteines 52 and 58. To verify the results obtained by docking, we carried out a molecular dynamics simulation with the compounds that presented the highest and lowest docking energies. The results showed that the root mean square deviation (RMSD) between the initial and final pose were very small. In addition, the hydrogen bond pattern was conserved along the simulation. In the parasite enzyme, the amino acid residues Leu399, Met400 and Lys402 are replaced in the human enzyme by Met406, Tyr407 and Ala409, respectively. In view of the fact that Leu399 is an amino acid of the Z site, this difference could be explored to design selective inhibitors of TR.

Dynamics at infinity and the existence of singularly degenerate heteroclinic cycles in the Lorenz system

In this paper, by using the Poincare compactification in R(3) we make a global analysis of the Lorenz system, including the complete description of its dynamic behavior on the sphere at infinity. Combining analytical and numerical techniques we show that for the parameter value b = 0 the system presents an infinite set of singularly degenerate heteroclinic cycles, which consist of invariant sets formed by a line of equilibria together with heteroclinic orbits connecting two of the equilibria. The dynamical consequences related to the existence of such cycles are discussed. In particular a possibly new mechanism behind the creation of Lorenz-like chaotic attractors, consisting of the change in the stability index of the saddle at the origin as the parameter b crosses the null value, is proposed. Based on the knowledge of this mechanism we have numerically found chaotic attractors for the Lorenz system in the case of small b > 0, so nearby the singularly degenerate heteroclinic cycles.

Oxygen dynamics and the effects of heat treatments in SBCO samples investigated by mechanical spectroscopy

The compound SmBa(2)Cu(3)O(7-delta) (SBCO)-obtained by substituting rare-earth Sm for Y in the well-known and most studied YBa(2)Cu(3)O(6+delta) (YBCO)-is potentially attractive to study in order to understand the superconductivity mechanism in physics and in electronic device applications. For SBCO, the possibility of variable stoichiometry and the high mobility of oxygen in CuO(x) planes give rise to a rich phase diagram. This study reports on the effect of heat treatments in an oxygen atmosphere on the anelastic properties of this oxide, in which relaxation processes were observed, attributed to oxygen atom jumps present in the Cu-O planes during the orthorhombic phase.

Dynamics of glyphosate-induced conformational changes of Mycobacterium tuberculosis 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19) determined by hydrogen-deuterium exchange and electrospray mass spectrometry

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the reaction between shikimate 3-phosphate and phosphoenolpyruvate to form 5-enolpyruvylshikimate 3-phosphate, an intermediate in the shikimate pathway, which leads to the biosynthesis of aromatic amino acids. EPSPS exists in an open conformation in the absence of substrates and/or inhibitors and in a closed conformation when bound to the substrate and/or inhibitor. In the present report, the H/D exchange properties of EPSPS from Mycobacterium tuberculosis (Mt) were investigated for both enzyme conformations using ESI mass spectrometry and circular dichroism (CD). When the conformational changes identified by H/D exchanges were mapped on the 3-D structure, it was observed that the apoenzyme underwent extensive conformational changes due to glyphosate complexation, characterized by an increase in the content of alpha-helices from 40% to 57%, while the beta-sheet content decreased from 30% to 23%. These results indicate that the enzyme underwent a series of rearrangements of its secondary structure that were accompanied by a large decrease in solvent access to many different regions of the protein. This was attributed to the compaction of 71% of alpha-helices and 57% of beta-sheets as a consequence of glyphosate binding to the enzyme. Apparently, MtEPSPS undergoes a series of inhibitor-induced conformational changes, which seem to have caused synergistic effects in preventing solvent access to the core of molecule, especially in the cleft region. This may be part of the mechanism of inhibition of the enzyme, which is required to prevent the hydration of the substrate binding site and also to induce the cleft closure to avoid entrance of the substrates.

Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel-like activity, and the role of the amidated C-terminus

Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of its C-terminus. Secondary structure determination, by circular dichroism spectroscopy in amphipathic environments, and lytic activity in zwitterionic and anionic vesicles showed quite similar results for the amidated and the carboxylated forms of the peptide. The deamidation of the C-terminus introduced a negative charge at an all-positive charged peptide, causing a loss of amphipathicity, as indicated by molecular dynamics simulations in TFE/water mixtures and this subtle modification in a peptide's primary structure disturbed the interaction with bilayers and biological membranes. Although being poorly lytic, the amidated form, but not the carboxylated, presented ion channel-like activity on anionic bilayers with a well-defined conductance step; at approximately the same concentration it showed antimicrobial activity. The pores remain open at trans-negative potentials, preferentially conducting cations, and this situation is equivalent to the interaction of the peptide with bacterial membranes that also maintain a high negative potential inside. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Dissipative dynamics of matter-wave solitons in a nonlinear optical lattice

Dynamics and stability of solitons in two-dimensional (2D) Bose-Einstein condensates (BEC), with one-dimensional (1D) conservative plus dissipative nonlinear optical lattices, are investigated. In the case of focusing media (with attractive atomic systems), the collapse of the wave packet is arrested by the dissipative periodic nonlinearity. The adiabatic variation of the background scattering length leads to metastable matter-wave solitons. When the atom feeding mechanism is used, a dissipative soliton can exist in focusing 2D media with 1D periodic nonlinearity. In the defocusing media (repulsive BEC case) with harmonic trap in one direction and nonlinear optical lattice in the other direction, the stable soliton can exist. Variational approach simulations are confirmed by full numerical results for the 2D Gross-Pitaevskii equation.

Effects of oscillatory behavior of the dipole function on the dissociation dynamics of the classical driven Morse oscillator

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dissipation as a mechanism of energy gain

Some properties of the annular billiard under the presence of weak dissipation are studied. We show, in a dissipative system, that the average energy of a particle acquires higher values than its average energy of the conservative case. The creation of attractors, associated with a chaotic dynamics in the conservative regime, both in appropriated regions of the phase space, constitute a generic mechanism to increase the average energy of dynamical systems.

In-flight and collisional dissipation as a mechanism to suppress Fermi acceleration in a breathing Lorentz gas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stickiness in a bouncer model: A slowing mechanism for Fermi acceleration

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dynamics of Tm-Ho energy transfer and deactivation of the F-3(4) low level of thulium in fluorozirconate glasses

The mechanism involved in the Tm3+ (F-3(4))-->Ho3+ (I-5(7)) energy transfer and Tm3+ (H-3(4), H-3(6))-->Tm3+ (F-3(4), F-3(4)) cross relaxation as a function of the donor and acceptor concentrations was investigated in Tm-Ho-codoped fluorozirconate glasses. The experimental transfer rates were determined for the Tm-->Ho energy transfer from the best fit of the acceptor luminescence decay using an expression which takes into account the Inokuti-Hirayama model and localized donor-to-acceptor interaction solution. The original acceptor solution derived from the Inokuti-Hirayama model fits well the acceptor luminescence transient only for low-concentrated systems. The results showed that a fast excitation diffusion that occurs in a very short time (t<Tm cross relaxation and Tm-->Ho energy transfer ions from H-3(4) and F-3(4) thulium states, respectively. (C) 2004 American Institute of Physics.

Using transient and steady state considerations to investigate the mechanism of loss of stability of a dynamical system

This work presents the complete set of features for solutions of a particular non-ideal mechanical system near the fundamental and near to a secondary resonance region. The system comprises a pendulum with a horizontally moving suspension point. Its motion is the result of a non-ideal rotating power source (limited power supply), acting oil the Suspension point through a crank mechanism. Main emphasis is given to the loss of stability, which occurs by a sequence of events, including intermittence and crisis, when the system reaches a chaotic attractor. The system also undergoes a boundary-crisis, which presents a different aspect in the bifurcation diagram due to the non-ideal supposition. (c) 2004 Published by Elsevier B.V.

The defocusing mechanism of isochronous resonances

We present a numerical study concerning the defocusing mechanism of isochronous resonance island chains in the presence of two permanent robust tori. The process is initialized and concluded through bifurcations of fixed points located on the robust tori. Our approach is based on a Hamiltonian system derived from the resonant normal form. Choosing a convenient parameter in this system, we are able to depict a comprehensive analysis of the dynamics of the problem. (c) 2004 Elsevier B.V. All rights reserved.

Dynamics of a piecewise-linear oscillator with limited power supply

We discuss dynamics of a vibro-impact system consisting of a cart with an piecewise-linear restoring force, which vibrates under driving by a source with limited power supply. From the point of view of dynamical systems, vibro-impact systems exhibit a rich variety of phenomena, particularly chaotic motion. In our analyzes, we use bifurcation diagrams, basins of attractions, identifying several non-linear phenomena, such as chaotic regimes, crises, intermittent mechanisms, and coexistence of attractors with complex basins of attraction. © 2009 by ASME.

On nonlinear dynamics in a free fluid surface of a tank excited by a non-ideal power source

We investigate the nonlinear oscillations in a free surface of a fluid in a cylinder tank excited by non-ideal power source, an electric motor with limited power supply. We study the possibility of parametric resonance in this system, showing that the excitation mechanism can generate chaotic response. Additionally, the dynamics of parametrically excited surface waves in the tank can reveal new characteristics of the system. The fluid-dynamic system is modeled in such way as to obtain a nonlinear differential equation system. Numerical experiments are carried out to find the regions of chaotic solutions. Simulation results are presented as phase-portrait diagrams characterizing the resonant vibrations of free fluid surface and the existence of several types of regular and chaotic attractors. We also describe the energy transfer in the interaction process between the hydrodynamic system and the electric motor. Copyright © 2011 by ASME.