Molecular models of protein targets from Mycobacterium tuberculosis

Structural characterization of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design since some of these proteins may be present in the bacterial genome, but absent in humans. Thus, metabolic pathways became potential targets for drug design. The motivation of this work is the fact that Mycobacterium tuberculosis is the cause of the deaths of millions of people in the world, so that the structural characterization of protein targets to propose new drugs has become essential. DBMODELING is a relational database, created to highlight the importance of methods of molecular modeling applied to the Mycobacterium tuberculosis genome with the aim of proposing protein-ligand docking analysis. There are currently more than 300 models for proteins from Mycobacterium tuberculosis genome in the database. The database contains a detailed description of the reaction catalyzed by each enzyme and their atomic coordinates. Information about structures, a tool for animated gif image, a table with a specification of the metabolic pathway, modeled protein, inputs used in modeling, and analysis methods used in this project are available in the database for download. The search tool can be used for reseachers to find specific pathways or enzymes.

Molecular models of NS3 protease variants of the Hepatitis C virus

Background: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis.

Application of abrupt cut-off models in the analysis of the capacitance spectra of conjugated polymer devices

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

Stability of breathers in simple mechanical models for DNA

This work studies through the Floquet theory the stability of breathers generated by the anti-continuous limit. We used the Peyrard-Bishop model for DNA and two kinds of nonlinear potential: the Morse potential and a potential with a hump. The comparison of their stability was done in function of the coupling parameter. We also investigate the dynamic behaviour of the system in stable and unstable regions. Qualitatively, the dynamic of mobile breathers resembles DNA.

Habitat selection and potential antiherbivore effects of Peucetia flava (Oxyopidae) on Solanum thomasiifolium (Solanaceae)

Several spider species use plants as shelter and foraging sites, but the relationships among these organisms are still poorly known. Lynx spiders of the genus Peucetia do not build webs, and many species live strictly in plants bearing glandular trichomes. Peucetia flava Keyserling 1877 inhabits Solanum thomasifolium in southeastern Brazil and usually preys on herbivores and other small insects adhered to the glandular trichomes of its host plant. To evaluate the potential anti-herbivore protection. of this spider species for S. thomasifolium, we glued termites used as herbivore models oil trichomes of S. thomasifolium and on neighboring plants lacking glandular trichomes. leaf miner damage and spider density were recorded for S. thomasifolium plants in July 1997. There was a positive relationship between plant size and spider density. The removal or termites in S. thomasifolium by P. flava was higher than ill plants without glandular trichomes. The leaf miner damage was negatively related to spider density. Our results Suggest that P. flava may be all important plant bodyguard in the defense of S. thomasifolium from its natural herbivores.

N=2 sigma models for Ramond-Ramond backgrounds

Using the U(4) hybrid formalism, manifestly N = (2,2) worldsheet supersymmetric sigma models are constructed for the type-IIB superstring in Ramond-Ramond backgrounds. The Kahler potential in these N = 2 sigma models depends on four chiral and antichiral bosonic superfields and two chiral and antichiral fermionic superfields. When the Kahler potential is quadratic, the model is a free conformal field theory which describes a flat ten-dimensional target space with Ramond-Ramond flux and non-constant dilaton. For more general Kahler potentials, the model describes curved target spaces with Ramond-Ramond flux that are not plane-wave backgrounds. Ricci-flatness of the Kahler metric implies the on-shell conditions for the background up to the usual four-loop conformal anomaly.

Dynamically induced spontaneous symmetry breaking in 3-3-1 models

We show that in SU(3)(C) circle times SU(3)(L) circle times U(1)(N) (3-3-1) models embedded with a singlet scalar playing the role of the axion, after imposing scale invariance, the breaking of Peccei-Quinn symmetry occurs through the one-loop effective potential for the singlet field. We, then, analyze the structure of spontaneous symmetry breaking by studying the new scalar potential for the model, and verify that electroweak symmetry breaking is tightly connected to the 3-3-1 breaking by the strong constraints among their vacuum expectation values. This offers a valuable guide to write down the correct pattern of symmetry breaking for multi-scalar theories. We also obtained that the accompanying massive pseudo-scalar, instead of acquiring mass of order of Peccei-Quinn scale as we would expect, develops a mass at a much lower scale, a consequence solely of the breaking via Coleman-Weinberg mechanism. (c) 2005 Published by Elsevier B.V.

Reconstruction of interacting dark energy models from parametrizations

Models with interacting dark energy can alleviate the cosmic coincidence problem by allowing dark matter and dark energy to evolve in a similar fashion. At a fundamental level, these models are specified by choosing a functional form for the scalar potential and for the interaction term. However, in order to compare to observational data it is usually more convenient to use parametrizations of the dark energy equation of state and the evolution of the dark matter energy density. Once the relevant parameters are fitted, it is important to obtain the shape of the fundamental functions. In this paper I show how to reconstruct the scalar potential and the scalar interaction with dark matter from general parametrizations. I give a few examples and show that it is possible for the effective equation of state for the scalar field to cross the phantom barrier when interactions are allowed. I analyze the uncertainties in the reconstructed potential arising from foreseen errors in the estimation of fit parameters and point out that a Yukawa-like linear interaction results from a simple parametrization of the coupling.

Study of the discovery potential of light custodians in a clean decay channel at the LHC

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

Deciphering the minimum of energy of some walking technicolor models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Generalized neighbor-interaction models induced by nonlinear lattices

It is shown that the tight-binding approximation of the nonlinear Schrodinger equation with a periodic linear potential and periodic in space nonlinearity coefficient gives rise to a number of nonlinear lattices with complex, both linear and nonlinear, neighbor interactions. The obtained lattices present nonstandard possibilities, among which we mention a quasilinear regime, where the pulse dynamics obeys essentially the linear Schrodinger equation. We analyze the properties of such models both in connection to their modulational stability, as well as in regard to the existence and stability of their localized solitary wave solutions.

Nonlinear two-field models from orbit equation deformations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Supergraph approach in a higher-order linear delta expansion calculation of the effective potential for F-type broken supersymmetry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

On non-linear dynamics and an optimal control synthesis of the action potential of membranes (ideal and non-ideal cases) of the Hodgkin-Huxley (HH) mathematical model

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

Labaditin, a cyclic peptide with rich biotechnological potential: preliminary toxicological studies and structural changes in water and lipid membrane environment

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)