Docking and small angle X-ray scattering studies of purine nucleoside phosphorylase

Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Molecular modeling databases: A new way in the search of protein targets for drug development

DBMODELING is a relational database of annotated comparative protein structure models and their metabolic, pathway characterization. It is focused on enzymes identified in the genomes of Mycobacterium tuberculosis and Xylella fastidiosa. The main goal of the present database is to provide structural models to be used in docking simulations and drug design. However, since the accuracy of structural models is highly dependent on sequence identity between template and target, it is necessary to make clear to the user that only models which show high structural quality should be used in such efforts. Molecular modeling of these genomes generated a database, in which all structural models were built using alignments presenting more than 30% of sequence identity, generating models with medium and high accuracy. All models in the database are publicly accessible at http://www.biocristalografia.df.ibilce.unesp.br/tools. DBMODELING user interface provides users friendly menus, so that all information can be printed in one stop from any web browser. Furthermore, DBMODELING also provides a docking interface, which allows the user to carry out geometric docking simulation, against the molecular models available in the database. There are three other important homology model databases: MODBASE, SWISSMODEL, and GTOP. The main applications of these databases are described in the present article. © 2007 Bentham Science Publishers Ltd.

A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Generic Bifurcations of Planar Filippov Systems via Geometric Singular Perturbations

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

A geometric interpretation for transmission real losses minimization through the optimal power flow and its influence on voltage collapse

This work presents an approach for geometric solution of an optimal power flow (OPF) problem for a two bus system (a slack and a PV busses). Additionally, the geometric relationship between the losses minimization and the increase of the reactive margin and, therefore, the maximum loading point, is shown. The algebraic equations for the calculation of the Lagrange multipliers and for the minimum losses value are obtained. These equations are used to validate the results obtained using an OPF program. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Improved geometric parameterisation techniques for continuation power flow

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Geographic variation in cranial shape in the Pumpkin Toadlet (Brachycephalus ephippium): A geometric analysis

The description of patterns of variation in any character system within well-defined species is fundamental for understanding lineage diversification and the identification of geographic units that represent opportunities for sustained evolutionary divergence. In this paper, we analyze intraspecific variation in cranial shape in the Pumpkin Toadlet, Brachycephalus ephippium-a miniaturized species composed of isolated populations on the slopes of the mountain ranges of southeastern Brazil. Shape variables were derived using geometric-statistical methods that describe shape change as localized deformations in a spatial framework defined by anatomical landmarks in the cranium of B. ephippium. By statistically weighting differences between landmarks that are not close together (changes at larger geometric scale), cranial variation among geographic samples of B. ephippium appears continuous with no obvious gaps. This pattern of variation is caused by a confounding effect between within-sample allometry and among-sample shape differences. In contrast, by statistically weighting differences between landmarks that are at close spacing (changes at smaller geometric scale), differences in shape within- and among-sample variation are not confounded, and a marked geographic differentiation among population samples of B. ephippium emerges. The observed pattern of geographic differentiation in cranial shape apparently cannot be explained as isolation-by-distance. This study provides the first evidence that the detection of morphological variation or lack thereof, that is, morphological conservatism, may be conditional on the scale of measurement of variation in shape within the methodological formalism of geometric morphometrics.

Molecular Docking and Molecular Dynamic Studies of Semi-Synthetic Piperidine Alkaloids as Acetylcholinesterase Inhibitors

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

Surface pressure-area isotherms for Langmuir monolayers and a docking molecular orientation of perylene tetracarboxylic derivatives on a water surface

The surface pressure-molecular area (pi-A) isotherms for Langmuir monolayers of four perylenetetracarboxylic (PTCD) derivatives, measured with varying subphase temperatures and compression speeds, are reported. The behavior of these PTCD derivatives at the water-air interface is modeled using the rigid docking method. This approach is the first attempt to model the molecular orientation of PTCD on the water surface to be compared with experimental Langmuir isotherms. Through this methodology, it would be possible to anticipate aggregation and determine if favorable spatial orientations of perylenes are generated on the water surface. The pi-A isotherm experiments show that these molecules can support high surface pressures, indicating strong packing on the water surface and that the isotherms are compression speed independent but temperature dependent. The molecular orientation and stacking was further examined in Langmuir-Blodgett (LB) monolayers deposited onto glass and glass coated with Ag island films using UV-visible absorption and surface-enhanced fluorescence (SEF) measurements.

Revisiting the addition reaction of TeCl4 to alkynes: the crystal structure and docking studies of 1-chloro-2-trichlorotelluro-3-phenyl-propen-2-ol

Tellurium tetrachloride adds to alkynes via two pathways: a concerted syn addition, that yields Z-tri- and tetra-substituted alkenes or by an anti addition that yields E-alkenes. The mechanistic aspects of these divergent pathways have been reevaluated at the light of crystallographic data. The molecules, of the title compound, in the crystal, are associated in a helical fashion with a Te...Te pitch of 6.3492(6) angstrom. As it exhibits inhibitory activity for cathepsin B and in order to gain more insight of the inhibition mechanism, a docking study was undertaken providing insight on why organic telluranes are more efficient inhibitors than inorganic ones as AS-101. (c) 2006 Elsevier B.V. All rights reserved.

An efficient geometric parameterization technique for the continuation power flow

Continuation methods have been shown as efficient tools for solving ill-conditioned cases, with close to singular Jacobian matrices, such as the maximum loading point of power systems. Some parameterization techniques have been proposed to avoid matrix singularity and successfully solve those cases. This paper presents a new geometric parameterization scheme that allows the complete tracing of the P-V curves without ill-conditioning problems. The proposed technique associates robustness to simplicity and, it is of easy understanding. The Jacobian matrix singularity is avoided by the addition of a line equation, which passes through a point in the plane determined by the total real power losses and loading factor. These two parameters have clear physical meaning. The application of this new technique to the IEEE systems (14, 30, 57, 118 and 300 buses) shows that the best characteristics of the conventional Newton's method are not only preserved but also improved. (C) 2006 Elsevier B.V. All rights reserved.

Conformational analyses and docking studies of a series of 5-nitrofuran- and 5-nitrothiophen-semicarbazone derivatives in three possible binding sites of trypanothione and glutathione reductases

To explore three possible binding sites of trypanothione and glutathione reductase, namely, the active, the dimer interface and the coenzyme NADPH binding site, a series of eight compounds, nitrofurans and nitrothiophenes derivatives, were docked, using their crystallographic and modeled conformations. Docking results showed that, for both families and both enzymes, compounds are more likely to bind in the interface site, even though there is some probability of binding in the active site. These studies are in agreement with experimental data, which suggest that these class of compounds can act either as uncompetitive or mixed type inhibitors, and also with the finding that there is an alpha-helix which connects the active with the interface site, thus allowing charge transference between them. (c) 2005 Elsevier B.V. All rights reserved.

The Geometric Birnbaum-Saunders regression model with cure rate

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Tensor3D: A computer graphics program to simulate 3D real-time deformation and visualization of geometric bodies

Tensor3D is a geometric modeling program with the capacity to simulate and visualize in real-time the deformation, specified through a tensor matrix and applied to triangulated models representing geological bodies. 3D visualization allows the study of deformational processes that are traditionally conducted in 2D, such as simple and pure shears. Besides geometric objects that are immediately available in the program window, the program can read other models from disk, thus being able to import objects created with different open-source or proprietary programs. A strain ellipsoid and a bounding box are simultaneously shown and instantly deformed with the main object. The principal axes of strain are visualized as well to provide graphical information about the orientation of the tensor's normal components. The deformed models can also be saved, retrieved later and deformed again, in order to study different steps of progressive strain, or to make this data available to other programs. The shape of stress ellipsoids and the corresponding Mohr circles defined by any stress tensor can also be represented. The application was written using the Visualization ToolKit, a powerful scientific visualization library in the public domain. This development choice, allied to the use of the Tcl/Tk programming language, which is independent on the host computational platform, makes the program a useful tool for the study of geometric deformations directly in three dimensions in teaching as well as research activities. (C) 2007 Elsevier Ltd. All rights reserved.

Refractive and geometric lens characterization through multi-wavelength digital speckle pattern interferometry

Physical parameters of different types of lenses were measured through digital speckle pattern interferometry (DSPI) using a multimode diode laser as light source. When such lasers emit two or more longitudinal modes simultaneously the speckle image of an object appears covered of contour fringes. By performing the quantitative fringe evaluation the radii of curvature as well as the refractive indexes of the lenses were determined. The fringe quantitative evaluation was carried out through the four- and the eight-stepping techniques and the branch-cut method was employed for phase unwrapping. With all these parameters the focal length was calculated. This whole-field multi-wavelength method does enable the characterization of spherical and aspherical lenses and of positive and negative ones as well. (C) 2007 Elsevier B.V. All rights reserved.