A abordagem de modos normais de baixa frequência na descrição das flutuações conformacionais dos estados nativos das proteínas globulares tem ajudado na caracterização das suas funções biológicas. Vários métodos teóricos e experimentais têm sido empregados para a determinação destas flutuações internas. Estes movimentos podem ser caracterizados pelo fator Debye-Waller (fator-B), correspondente à mobilidade local do resíduo em nível atômico. A análise de modos normais utilizando os modelos de rede elástica (ENM) demonstra ser uma técnica robusta. Fatores-B experimentais são reproduzidos teoricamente por meio desta técnica em tempos computacionais relativamente curtos, mostrando-se competitiva com as técnicas mais sofisticadas. O modelo de rede elástica é uma abordagem t ipo coarse-grain na qual a proteína no seu estado enovelado é representada por uma rede elástica tridimensional de carbonos conectados por molas. As molas representam as interações ligantes e não ligantes entre os carbonos . Neste trabalho, inicialmente, estudamos os modelos de rede elástica já conhecidos na literatura. Em seguida, realizamos um estudo comparativo entre eles. Neste estudo, comprovamos que os modelos pfGNM e pfANM apresentam melhor correlação com os fatores-B experimentais que os os modelos GNM e ANM tradicionais. Desenvolvemos também uma nova abordagem, a qual intitulamos número de contatos ponderados anisotrópica (AWCN). Mostramos que a abordagem AWCN apresenta um desempenho significativamente melhor que o modelo de rede elástica anisotrópica tradicional. Por fim, realizamos um estudo de caráter investigativo do comportamento do peso das interações entre resíduos. Este estudo re velou que, para os modelos WCN e AWCN, a correlação exibe o seu valor máximo para interações ponderadas $1/R^p$, entre resíduos $i$ e $j$j, para valores de $p$ em torno de 2. Nos modelos pfGNM e pfANM a correlação é maximizada para dois valores de $p$, o primeiro em torno de 2 e o segundo em torno de 4,75, indicando que a ponderação pelo recíproco do quadrado da distância, usualmente empregada na literatura, pode não ser adequada para obter a melhor correlação. / Low frequency normal mode approach to describe conformational fluctuations of globular proteins has helped to characterize their biological functions. Various theoretical and experimental methods have been employed to det ermine the magnitudes of those internal motions. Those motions can be characterized by the Debye-Waller factor (B-factor), co rresponding to the local mobility of the residue at the atomic level. Normal mode analysis using elastic network models (ENM) has demonstrated to be a robust technique. Experimental B-factors has been reproduced theoretically by means of this techniq ue in a short computational time and it has been shown to be competitive with more sophisticated techniques. The ENM is a coarse-grained approach in which the protein is represented by a three-dimensional elastic network of alpha-carbon atoms connect ed by springs. Springs represent bonded and non-bonded interactions between the alpha-carbon atoms. In this work, we study th e elastic network models known in the literature. Next, we perform a comparative study between them. We show that the pfGNM a nd pfANM models present better correlation with experimental B-factors than the traditional GNM and ANM models. We also devel op a new approach, which we entitled anisotropic weighted contact number (AWCN). We show that it presents results significantly better than the traditional anisotropic elastic network model. Finally, we perform a study of investigative character of the behavior for the weight of the interactions between residues. This study revealed that, for the WCN and AWCN models, the correlation exhibits its maximum value for weighted interactions $1/R^p$, between residues $i$ and $j$, for values of $p$ around 2. In the pfGNM and pfANM models the correlation is max imized for two values of $p$, the first one around 2 and the second one around 4.75. This indicates that the weighting by the reciprocal of the square of the distance, usually employed in the literature, may not be appropriate to obtain the best correlation.

Wave propagation problems can be modeled by partial differential equations. In this thesis, we study wave propagation in fluids and in solids, modeled by the acoustic wave equation and the elastic wave equation, respectively. In real-world applications, waves often propagate in heterogeneous media with complex geometries, which makes it impossible to derive exact solutions to the governing equations. Alternatively, we seek approximated solutions by constructing numerical methods and implementing on modern computers. An efficient numerical method produces accurate approximations at low computational cost. There are many choices of numerical methods for solving partial differential equations. Which method is more efficient than the others depends on the particular problem we consider. In this thesis, we study two numerical methods: the finite difference method and the discontinuous Galerkin method. The finite difference method is conceptually simple and easy to implement, but has difficulties in handling complex geometries of the computational domain. We construct high order finite difference methods for wave propagation in heterogeneous media with complex geometries. In addition, we derive error estimates to a class of finite difference operators applied to the acoustic wave equation. The discontinuous Galerkin method is flexible with complex geometries. Moreover, the discontinuous nature between elements makes the method suitable for multiphysics problems. We use an energy based discontinuous Galerkin method to solve a coupled acoustic-elastic problem.

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This master thesis deals with VUT~081~Kondor aircraft flutter analysis. This aircraft is being designed at the Institute of Aerospace Engineering, Faculty of Mechanical Engineering, Brno University of Technology. The thesis contains detailed aircraft description, natural frequency and normal modes computation as well as aircraft structure flutter analysis and critical flutter velocity determination. Some structure improvement recommendations have been given in order to increase the critical flutter velocity and to fulfil the CS-VLA regulation requirements.

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are inhibited by nerve agents such as sarin and tabun. In general, the inhibited enzymes are reactivated by bisquaternary ammonium compounds (oximes). The binding free energies of the oximes; 2-PAM, MMB-4, HI-6, and obidoxime bound to human AChE (hAChE) and human BChE (hBChE) inhibited by sarin and tabun and also to the uninhibited enzymes were calculated using various computational methods. Using thermodynamic integration, the binding free energies of all the inhibited and uninhibited systems of MMB-4 and obidoxime were evaluated. The standard binding free energies (dA) were more negative than the experimental values due to limitations of the ff99 forcefield. The RMS error of dA for the inhibited systems of MMB-4 was 2.1 kcal/mol, and for obidoxime systems it was 4.8 kcal/mol with respect to the experimental free energies. The binding enthalpies calculated using MM-GBSA and MM-PBSA methods for 2-PAM, MMB-4, HI-6, and obidoxime systems were negative, except for hBChE-sarin-MMB-4 and hBChE-sarin-obidoxime. For all the systems the TdS values calculated using normal mode analysis were equal to or lower in magnitude than their corresponding binding enthalpies. As a result, the estimated free energies were positive for most of the systems. Clearly, the present algorithms cannot effectively estimate the binding entropies for a protein-ligand system. Met81 has commonly shown favorable interactions, and lysine or arginine exhibited unfavorable interactions with the reactivator in all the systems. Second, the interactions between chloropyrifos-oxon (Cpo) and experimentally tested neutral and monopyridinium oximes bound to the Q192 or R192 polymorphs of human paraoxonase1 (hPON1) were studied. The equilibrated Q192 and R192 hPON1 were structurally different than the crystal structure of recombinant PON1. The neutral oximes have shown more favorable interactions with Cpo in Q192 hPON1 + Cpo system compared to R192 hPON1 + Cpo. Whereas the monopyridinium oximes interacted more affectively with Cpo in R192 hPON1 than Q192 hPON1. The relative deprotonation energy of the monopyridinium oxime was lower than the neutral oxime. Hence, the monopyridinium oxime can hydrolyze an organophosphate at a higher rate than a neutral oxime.

In this thesis we have employed two computational approaches, temperature-dependent molecular dynamics (MD) and normal mode analysis (NMA), to gain insights into the structureunction relationships between three structurally-related proteins, each possessing a central alpha/beta core. The three proteins studied here are: pnbCE from Bacillus subtilis, cutinase from Fusarium solani - both belong to the serine hydrolase family - and TTHA1554, from the thermophile Thermus thermophilus. Mutations at the gate residue 362, located at the side-door of the pnbCE enzyme, are known to alter the catalytic activity of this enzyme. In this work the modifications induced by mutating LEU362 on the structural and dynamical properties of pnbCE are also explored. From MD simulations at several temperatures, we propose a mechanism by which mutations at position 362 of pnbCE affect the stability and functionality of this enzyme. We have identified two coil residues, SER218 and GLN276, whose interactions with residue 362 in wild-type and mutant pnbCE enzymes control the dynamics of the side-door domain of pnbCE. A hydrogen bond between the GLN276 and ARG362 residues in the arginine substituted (L362R) pnbCE mutant enzyme appears to be responsible for locking the sidedoor domain region of the L362R enzyme, thus lowering the catalytic rates of the L362R mutant pnbCE enzyme compared to the wild-type. Similarly, a hydrogen bond formed between SER218 and ARG362 in L362R provides thermal stability to the arginine substituted mutant enzyme. This hydrogen bond is not as prevalent in the wild-type or other mutated pnbCEs, making them prone to structural fluctuations upon increasing temperature. The predominant lowrequency mode, obtained from normal mode analysis, reveals a collective scissor-like motion of residues surrounding the openings to the active site that validates the results of MD simulations on pnbCE systems. The collective motion of large loops also appear in the lowrequency modes of cutinase and TTHA1554, which correspond to particularly mobile regions in these proteins. An attempt to locate a putative active site of the thermophilic protein TTHA1554 was inconclusive. In general, useful comparisons of the flexibility, stability, and dynamic changes were calculated for the three selected proteins.

This study proposed a finite element procedure for protein normal mode analysis (NMA). The finite element model adopted the protein solvent-excluded surface to generate a homogeneous and isotropic volume. A simplified triangular approximation of coarse molecular surface was generated from the original surface model by using the Gaussian-based blurring technique. Similar to the widely adopted elastic network model, the finite element model holds a major advantage over standard all-atom normal mode analysis: the computationally expensive process of energy minimization that may distort the initial protein structure has been eliminated. This modification significantly increases the efficiency of normal mode analysis. In addition, the finite element model successfully brings out the capability of normal mode analysis in low-frequency/high collectivity molecular motion by capturing protein shape properties. Fair results from six protein models in this study have fortified the capability of the finite element model in protein normal mode analysis.

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No description available.

No / An investigation of the surface current distribution in a normal-mode helical antenna (NMHA) is reported. This enables precise prediction of the performance of NMHAs, since traditional wire-antenna simulations ignore important details, such as non-uniform and transverse current distributions. A moment-method formulation is developed, using two-dimensional basis functions to represent the total non-uniform surface current distribution over the surface of the wire of the helix. Piecewise-sinusoidal basis functions are employed in two normal directions, with an exact kernel formulation and application of Galerkin's solution method. The numerical solution of the singular integrals associated with self-impedance terms was computed with a very low relative error. The surface current distribution was computed for different helix geometries. It was found that the axially-directed component of the current distribution around the surface of the wire was highly non-uniform and that there was also a significant circumferential current flow due to inter-turn capacitance, both effects that are overlooked by standard filamentary current representations.