Estudo in silico da interação da albumina de soro humano com o ibuprofeno

Currently, computational methods have been increasingly used to aid in the characterization of molecular biological systems, especially when they relevant to human health. Ibuprofen is a nonsteroidal antiinflammatory or broadband use in the clinic. Once in the bloodstream, most of ibuprofen is linked to human serum albumin, the major protein of blood plasma, decreasing its bioavailability and requiring larger doses to produce its antiinflamatory action. This study aimes to characterize, through the interaction energy, how is the binding of ibuprofen to albumin and to establish what are the main amino acids and molecular interactions involved in the process. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant ε = 40 was used. The findings corroborate the literature in which the Sudlow site I (I-FA3) is the primary binding site and the site I-FA6 as secondary site. However, it differs in identifying the most important amino acids, which by interaction energy, in order of decreasing energy, are: Arg410, Lys414, Ser 489, Leu453 and Tyr411 to the I-Site FA3 and Leu481, Ser480, Lys351, Val482 and Arg209 to the site I-FA6. The quantification of interaction energy and description of the most important amino acids opens new avenues for studies aiming at manipulating the structure of ibuprofen, in order to decrease its interaction with albumin, and consequently increase its distribution

Sistemas Nanoestruturados: Heteroestruturas Quasi-Periódicas de Nitretos e Cálculos Ab initio em Polimorfos CaCO3

The physical properties and the excitations spectrum in oxides and semiconductors materials are presented in this work, whose the first part presents a study on the confinement of optical phonons in artificial systems based on III-V nitrides, grown in periodic and quasiperiodic forms. The second part of this work describes the Ab initio calculations which were carried out to obtain the optoeletronic properties of Calcium Oxide (CaO) and Calcium Carbonate (CaCO3) crystals. For periodic and quasi-periodic superlattices, we present some dynamical properties related to confined optical phonons (bulk and surface), obtained through simple theories, such as the dielectric continuous model, and using techniques such as the transfer-matrix method. The localization character of confined optical phonon modes, the magnitude of the bands in the spectrum and the power laws of these structures are presented as functions of the generation number of sequence. The ab initio calculations have been carried out using the CASTEP software (Cambridge Total Sequential Energy Package), and they were based on ultrasoft-like pseudopotentials and Density Functional Theory (DFT). Two di®erent geometry optimizations have been e®ectuated for CaO crystals and CaCO3 polymorphs, according to LDA (local density approximation) and GGA (generalized gradient approximation) approaches, determining several properties, e. g. lattice parameters, bond length, electrons density, energy band structures, electrons density of states, e®ective masses and optical properties, such as dielectric constant, absorption, re°ectivity, conductivity and refractive index. Those results were employed to investigate the confinement of excitons in spherical Si@CaCO3 and CaCO3@SiO2 quantum dots and in calcium carbonate nanoparticles, and were also employed in investigations of the photoluminescence spectra of CaCO3 crystal

Estudo in silico das interações da protease NS3-NS2B de DENV-2 com o inibidor peptídico Bz-nKRR-H com finalidades terapêuticas

Dengue virus is an important patogen that causes Dengue desease in all world, and belongs to Flavivirus gender. The virus consists of enveloped RNA with a single strand positive sense, 11Kb genome. The RNA is translated into a polyprotein precursor, wich is cleaved into 3 structural proteins (C, prM e E) and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B e NS5). The NS3 is a multifunctional protein, that besides to promote the polyprotein precursor cleavage, also have NTPase, helicase and RTPase activity. The NS3 needs a hydrophilic segment of 40 residues from the transmembrane NS2B protein (who acts like cofator) to realize this functions. Actually, there's no vacines available on the market, and the treatment are just symptomatic. The tetrapeptide inhibitor Bz-Nle-Lys-Arg-Arg-H (Ki de 5,8-7,0 M) was showed as a potent inhibitor μ for NS3prot in Dengue virus. That is a inteligent alternative to treat the dengue desease. The present work aimed analyse the interactions of the ligand bounded to the activity site to provid a clear and depth vision of that interaction. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant = 20 ε and 80 was used. The results demonstrate that the interaction energy of the system reached convergence at 13.5 A. Within a radius of 13,5A the most important residues were identified. Met49, Met84 and Asp81 perform interactions of hydrogen with the ligant. The Asp79 and Asp75 residues present high energy of attraction. Arg54, Arg85 and Lys 131 perform hydrogen interactions with the ligand, however, appear in BIRD graph having high repulsion energy with the inhibitor. The data also emphasizes the importance of residue Tyr161 and the involvement of the catalytic triad composed by Asp75, His51 and Ser135

Análise e desenvolvimento de controladores preditivos multivariáveis baseados em multi-modelos bilineares

This work addresses issues related to analysis and development of multivariable predictive controllers based on bilinear multi-models. Linear Generalized Predictive Control (GPC) monovariable and multivariable is shown, and highlighted its properties, key features and applications in industry. Bilinear GPC, the basis for the development of this thesis, is presented by the time-step quasilinearization approach. Some results are presented using this controller in order to show its best performance when compared to linear GPC, since the bilinear models represent better the dynamics of certain processes. Time-step quasilinearization, due to the fact that it is an approximation, causes a prediction error, which limits the performance of this controller when prediction horizon increases. Due to its prediction error, Bilinear GPC with iterative compensation is shown in order to minimize this error, seeking a better performance than the classic Bilinear GPC. Results of iterative compensation algorithm are shown. The use of multi-model is discussed in this thesis, in order to correct the deficiency of controllers based on single model, when they are applied in cases with large operation ranges. Methods of measuring the distance between models, also called metrics, are the main contribution of this thesis. Several application results in simulated distillation columns, which are close enough to actual behaviour of them, are made, and the results have shown satisfactory

Estudo e implementação em plantas físicas de um controlador preditivo generalizado com restrições

This work shows a study about the Generalized Predictive Controllers with Restrictions and their implementation in physical plants. Three types of restrictions will be discussed: restrictions in the variation rate of the signal control, restrictions in the amplitude of the signal control and restrictions in the amplitude of the Out signal (plant response). At the predictive control, the control law is obtained by the minimization of an objective function. To consider the restrictions, this minimization of the objective function is done by the use of a method to solve optimizing problems with restrictions. The chosen method was the Rosen Algorithm (based on the Gradient-projection). The physical plants in this study are two didactical systems of water level control. The first order one (a simple tank) and another of second order, which is formed by two tanks connected in cascade. The codes are implemented in C++ language and the communication with the system to be done through using a data acquisition panel offered by the system producer

Análise da magnetohidrodinâmica com transferência de calor em canais de placas paralelas via transformação integral

The main goal of the present work is related to the dynamics of the steady state, incompressible, laminar flow with heat transfer, of an electrically conducting and Newtonian fluid inside a flat parallel-plate channel under the action of an external and uniform magnetic field. For solution of the governing equations, written in the parabolic boundary layer and stream-function formulation, it was employed the hybrid, numericalanalytical, approach known as Generalized Integral Transform Technique (GITT). The flow is sustained by a pressure gradient and the magnetic field is applied in the direction normal to the flow and is assumed that normal magnetic field is kept uniform, remaining larger than any other fields generated in other directions. In order to evaluate the influence of the applied magnetic field on both entrance regions, thermal and hydrodynamic, for this forced convection problem, as well as for validating purposes of the adopted solution methodology, two kinds of channel entry conditions for the velocity field were used: an uniform and an non-MHD parabolic profile. On the other hand, for the thermal problem only an uniform temperature profile at the channel inlet was employed as boundary condition. Along the channel wall, plates are maintained at constant temperature, either equal to or different from each other. Results for the velocity and temperature fields as well as for the main related potentials are produced and compared, for validation purposes, to results reported on literature as function of the main dimensionless governing parameters as Reynolds and Hartman numbers, for typical situations. Finally, in order to illustrate the consistency of the integral transform method, convergence analyses are also effectuated and presented

Otimização topológica de estruturas termoelásticas tridimensionais

This work presents an optimization technique based on structural topology optimization methods, TOM, designed to solve problems of thermoelasticity 3D. The presented approach is based on the adjoint method of sensitivity analysis unified design and is intended to loosely coupled thermomechanical problems. The technique makes use of analytical expressions of sensitivities, enabling a reduction in the computational cost through the use of a coupled field adjoint equation, defined in terms the of temperature and displacement fields. The TOM used is based on the material aproach. Thus, to make the domain is composed of a continuous distribution of material, enabling the use of classical models in nonlinear programming optimization problem, the microstructure is considered as a porous medium and its constitutive equation is a function only of the homogenized relative density of the material. In this approach, the actual properties of materials with intermediate densities are penalized based on an artificial microstructure model based on the SIMP (Solid Isotropic Material with Penalty). To circumvent problems chessboard and reduce dependence on layout in relation to the final optimal initial mesh, caused by problems of numerical instability, restrictions on components of the gradient of relative densities were applied. The optimization problem is solved by applying the augmented Lagrangian method, the solution being obtained by applying the finite element method of Galerkin, the process of approximation using the finite element Tetra4. This element has the ability to interpolate both the relative density and the displacement components and temperature. As for the definition of the problem, the heat load is assumed in steady state, i.e., the effects of conduction and convection of heat does not vary with time. The mechanical load is assumed static and distributed

Estatística não-extensiva aplicada ao cálculo do calor específico eletrônico em estruturas quasiperiódicas

Systems whose spectra are fractals or multifractals have received a lot of attention in recent years. The complete understanding of the behavior of many physical properties of these systems is still far from being complete because of the complexity of such systems. Thus, new applications and new methods of study of their spectra have been proposed and consequently a light has been thrown on their properties, enabling a better understanding of these systems. We present in this work initially the basic and necessary theoretical framework regarding the calculation of energy spectrum of elementary excitations in some systems, especially in quasiperiodic ones. Later we show, by using the Schr¨odinger equation in tight-binding approximation, the results for the specific heat of electrons within the statistical mechanics of Boltzmann-Gibbs for one-dimensional quasiperiodic systems, growth by following the Fibonacci and Double Period rules. Structures of this type have already been exploited enough, however the use of non-extensive statistical mechanics proposed by Constantino Tsallis is well suited to systems that have a fractal profile, and therefore our main objective was to apply it to the calculation of thermodynamical quantities, by extending a little more the understanding of the properties of these systems. Accordingly, we calculate, analytical and numerically, the generalized specific heat of electrons in one-dimensional quasiperiodic systems (quasicrystals) generated by the Fibonacci and Double Period sequences. The electronic spectra were obtained by solving the Schr¨odinger equation in the tight-binding approach. Numerical results are presented for the two types of systems with different values of the parameter of nonextensivity q

Ondas de spin em quasi-cristais magnônicos

In this paper we investigate the spectra of band structures and transmittance in magnonic quasicrystals that exhibit the so-called deterministic disorders, specifically, magnetic multilayer systems, which are built obeying to the generalized Fibonacci (only golden mean (GM), silver mean (SM), bronze mean (BM), copper mean (CM) and nickel mean (NM) cases) and k-component Fibonacci substitutional sequences. The theoretical model is based on the Heisenberg Hamiltonian in the exchange regime, together with the powerful transfer matrix method, and taking into account the RPA approximation. The magnetic materials considered are simple cubic ferromagnets. Our main interest in this study is to investigate the effects of quasiperiodicity on the physical properties of the systems mentioned by analyzing the behavior of spin wave propagation through the dispersion and transmission spectra of these structures. Among of these results we detach: (i) the fragmentation of the bulk bands, which in the limit of high generations, become a Cantor set, and the presence of the mig-gap frequency in the spin waves transmission, for generalized Fibonacci sequence, and (ii) the strong dependence of the magnonic band gap with respect to the parameters k, which determines the amount of different magnetic materials are present in quasicrystal, and n, which is the generation number of the sequence k-component Fibonacci. In this last case, we have verified that the system presents a magnonic band gap, whose width and frequency region can be controlled by varying k and n. In the exchange regime, the spin waves propagate with frequency of the order of a few tens of terahertz (THz). Therefore, from a experimental and technological point of view, the magnonic quasicrystals can be used as carriers or processors of informations, and the magnon (the quantum spin wave) is responsible for this transport and processing