In this thesis a computational complement to experimental observables will be presented. Computational tools such as molecular dynamics and quantum chemical tools will be used to aid in the interpretation of experimentally (NMR) obtained structural data. The techniques are applied to study the dynamical features of biologically important carbohydrates and their interaction with proteins. When evaluating conformations, molecular mechanical methods are commonly used. Paper I, highlights some important considerations and focuses on the force field parameters pertaining to carbohydrate moieties. Testing of the new parameters on a trisaccharide showed promising results. In Paper II, a conformational analysis of a part of the repeating unit of a Shigella flexneri bacterium lipopolysaccharide using the modified force field revealed two major conformational states. The results showed good agreement with experimental data. In Paper III, a trisaccharide using Langevin dynamics was investigated. The approach used in the population analysis included a least-square fit technique to match T1 elaxation parameters. The results showed good agreement with experimental T-ROE build-up curves, and three states were concluded to be involved. In Paper IV, carbohydrate moieties were used in the development of prodrug candidates, to “hide” peptide opioid receptor agonists. Langevin dynamics and quantum chemical methods were employed to elucidate the structural preference of the compound. The results showed a chemical shift difference between hydrogens across the ring for the two isomers as well as a difference in the coupling constant, when taking the dynamics into account. In Paper V, the interaction of the Salmonella enteritidis bacteriophage P22 with its host bacterium, involves an initial hydrolysis of the O-antigenic polysaccharide (O-PS). Docking calculations were used to examine the binding between the Phage P22 tail-spike protein and the O-PS repeating unit. Results indicated a possible active site in conjunction with NMR measurements.

Despite numerous advances in experimental methodologies capable of addressing the various phenomenon occurring on metal surfaces, atomic scale resolution of the microscopic dynamics remains elusive for most systems. Computational models of the processes may serve as an alternative tool to fill this void. To this end, parallel molecular dynamics simulations of self-diffusion on metal surfaces have been developed and employed to address microscopic details of the system. However these simulations are not without their limitations and prove to be computationally impractical for a variety of chemically relevant systems, particularly for diffusive events occurring in the low temperature regime. To circumvent this difficulty, a corresponding coarse-grained representation of the surface is also developed resulting in a reduction of the required computational effort by several orders of magnitude, and this description becomes all the more advantageous with increasing system size and complexity. This representation provides a convenient framework to address fundamental aspects of diffusion in nonequilibrium environments and an interesting mechanism for directing diffusive motion along the surface is explored. In the ensuing discussion, additional topics including transition state theory in noisy systems and the construction of a checking function for protein structure validation are outlined. For decades the former has served as a cornerstone for estimates of chemical reaction rates. However, in complex environments transition state theory most always provides only an upper bound for the true rate. An alternative approach is described that may alleviate some of the difficulties associated with this problem. Finally, one of the grand challenges facing the computational sciences is to develop methods capable of reconstructing protein structure based solely on readily-available sequence information. Herein a checking function is developed that may prove useful for addressing whether a particular proposed structure is a viable possibility.

The folding mechanism of several β-structures (e.g., β-hairpins and β-sheets) was studied using newly developed enhanced sampling methods along with MD simulations in all implicit solvent environments. The influence of different implicit solvent models on the folding simulation of β-structure was also tested. Through the analysis of the free energy landscape as the function of several suitable reaction coordinates, we observed that the folding of β-hairpins is actually a two-state transition. In addition, the folding free energy landscapes for those related hairpins indicate the apparent sequence dependence, which demonstrates different folding mechanisms of similar β-structures of varied sequence. We also found that the stability of backbone hydrogen bonds is determined by the turn sequence and the composition of hydrophobic core cluster in β-structures. Neither of these findings was reported before. The processive movement of kinesin was also studied at the mesoscopic level. We developed a simple physical model to understand the asymmetric hand-over-hand mechanism of the kinesin walking on the microtubule. The hand-over-hand motion of the conventional kinesin is reproduced in our model and good agreement is achieved between calculated and experimental results. The experimentally observed limping of the truncated kinesin is also perfectly described by our model. The global conformational change of kinesin heads (e.g., the power stroke of neck-linkers which works as lever-arms during the kinesin walking, the transition between open and closed states of the switch region of the nucleotide binding domain in each head induced by the nucleotide binding and release) was studied for both dimeric and monomeric kinesins using a coarse-grained model, anisotropic network model (ANM). At the same time Langevin mode analysis was used to study the solvent influence on the motions of the kinesin head mimicked by ANM. Additionally, the correlation between the neck-linker and the nucleotide binding site was also studied for dimeric and monomeric kinesins. The former shows the apparent correlation between two subdomains whereas the latter does not, which may explain the experimental observation that only the dimeric kinesin is capable of walking processively on the microtubule.

In this thesis, we investigate the quantum mechanical interaction of light with matter in the form of a gas of ultracold atoms: the atomic ensemble. We present a theoretical analysis of two problems, which involve the interaction of quantized electromagnetic fields (called signal and idler) with the atomic ensemble (i) cascade two-photon emission in an atomic ladder configuration, and (ii) photon frequency conversion in an atomic diamond configuration. The motivation of these studies comes from potential applications in long-distance quantum communication where it is desirable to generate quantum correlations between telecommunication wavelength light fields and ground level atomic coherences. In the two systems of interest, the light field produced in the upper arm of an atomic Rb level scheme is chosen to lie in the telecom window. The other field, resonant on a ground level transition, is in the near-infrared region of the spectrum. Telecom light is useful as it minimizes losses in the optical fiber transmission links of any two long-distance quantum communication device. We develop a theory of correlated signal-idler pair correlation. The analysis is complicated by the possible generation of multiple excitations in the atomic ensemble. An analytical treatment is given in the limit of a single excitation assuming adiabatic laser excitations. The analysis predicts superradiant timescales in the idler emission in agreement with experimental observation. To relax the restriction of a single excitation, we develop a different theory of cascade emission, which is solved by numerical simulation of classical stochastic differential equation using the theory of open quantum systems. The simulations are in good qualitative agreement with the analytical theory of superradiant timescales. We further analyze the feasibility of this two-photn source to realize the DLCZ protocol of the quantum repeater communication system. We provide a quantum theory of near-infrared to telecom wavelength conversion in the diamond configuration. The system provides a crucial part of a quantum-repeater memory element, which enables a "stored" near-infrared photon to be converted to a telecom wavelength for transmission without the destruction of light-atom quantum correlation. We calculate the theoretical conversion efficiency, analyzing the role of optical depth of the ensemble, pulse length, and quantum fluctuations on the process.

No description available.

En mécanique statistique quantique, un système quantique ouvert représente un petit système de degré fini de liberté en interaction avec un système extérieur très large (bain thermique, réservoir bosonique, environnement... ).<br /> <br /> Pour décrire cette interaction, les physiciens et les mathématiciens utilisent souvent deux approches: l'approche markovienne et l'approche hamiltonienne.<br /> <br /> Nous comparons systématiquement les approches hamiltonienne et markovienne dans les cas des modèles de spin-boson et de Pauli-Fierz. Ensuite, nous présentons un modèle lindbladien pour une chaîne de N spins couplée à des bains thermiques. Puis, nous étudions le lien entre les interactions quantiques répétées et la limite de densité faible. Finalement, nous étudions les propriétés des équations d'évolutions discrètes associées aux modèles d'interactions répétées, qui sont dirigées par des bruits discrets classiques.

Techn. Universiẗat, Diss., 2006--Darmstadt.

The repertoire of cellular functions mediated by Ribonucleic acid (RNA) molecules have expanded considerably during the last two decades. The role played by RNA in controlling and regulating gene expression in viruses, prokaryotes and eukaryotes has been a matter of continuous investigations. This interest has arisen primarily due to the discoveries of cisacting RNA structures like riboswitches, ribosensors and frameshift elements, which are found in either the 5’-, 3’-untranslated regions of mRNA or in the open reading frames. These structures control gene expression at the level of translation by either sequestering the Shine-Dalgarno (SD) sequence to regulate translation initiation or modulating ribosomal positions during an active translation process. Very often, these structures comprise of an RNA pseudoknot and it has been observed that these pseudoknots exist in a dynamic equilibrium with other intermediate structures. This equilibrium could be shifted by several factors including presence of ions, metabolites, temperature and external force. RNA pseudoknots represent the most versatile and ubiquitous class of RNA structures in the cell, whose unique folding topology could be exploited in a number of ways by the cellular machinery. In this thesis, a thorough study of programmed -1 ribosomal frameshifting (-1 PRF) process, which is a well known gene regulation event employed by many RNA viruses, was carried out. -1 PRF is a translation recoding process, necessary for viruses to main-tain a stoichiometric ratio of structural: enzymatic proteins. This ratio varies among different viral species. At the heart of this process, lies an RNA pseudoknot accompanied by a seven nucleotide long sequence motif, which pauses an actively translating ribosome on mRNA and causes it to shift its reading frame. The frameshift inducing efficiency of pseudoknot depends on multiple factors, for example the time scale of ribosomal pause and RNA unfolding, subsequent refolding of structure to native/intermediate states and/or environment conditions. With the aim of illustrating the fundamentals of the process, multiple factors involved in -1 PRF were studied. Chapters 2-4 represent distinct aspects of -1 PRF process, while Chapter 5 discusses a different work concerned with nucleocytoplasmic transport of tRNA carried out by nuclear export receptor Exporting. Chapter 1 gives an overview of the different regulatory activities with which RNA structures and sequences are found to be associated and the evolution of these stud-ies. It discusses the different types of structural motifs found to constitute tertiary RNA structure and secondary structure prediction and determination techniques. A brief description of ab initio RNA structure modeling and other relevant tools and methodologies used in this work has been presented. Details of techniques used in each study have been provided in relevant chapters. Chapter 2 describes how local factors like ionic conditions, hydration patterns, presence of protonated residues and single residue mutations affect the structural dynamics of an RNA pseudoknot involved in -1 PRF from a plant luteovirus. Single residue mutations in the loop regions or certain base-pair inversions in the stem regions of pseudoknot increase the frameshift inducing ability of the pseudoknot structure, while some others decrease this efficiency. However, it was not clear how the changes made to the wild-type (WT) RNA pseudoknot from Beet Western Yellow Mosaic virus were affecting the global structure in terms of its dynamics and other parameters. To study this, multiple all-atom molecular dynamics simulations (MD) were performed on WT and mutant structures created in silico. The effect of presence and absence of magnesium ions on the structural geometry was also studied. The analysis was done to identify the increase/decrease in the number of hydrogen bonds formed by Watson-Crick base-pairs in stem region or non Watson-Crick pairs between stem and loop. Ionic and water densities were analyzed and the role of potential ribosome-pseudoknot interaction was elaborated. With the aim of mimicking ribosome induced unfolding of an RNA pseudoknot, steered molecular dynamics pulling experiments were performed. This work was done primarily to understand the unfolding pathway of Hairpin(H)-type pseudoknots in general and the intermediate structures formed. Chapter 3 describes the thermodynamics and mechanics associated with the mechanical pulling of -1 PRF inducing RNA pseudoknot and its mutants described in previous chapter. Analysis of the trajectories reveal relative unfolding patterns in terms of disruption of various hydrogen bonds. This study allowed us to pinpoint the kind of intermediate structures being formed during pulling and whether these intermediate structures correspond to any known secondary structures, such as simple stem-loops. This information could be used for gaining insights into the folding pathways of these structures. An RNA pseudoknot stimulates -1 PRF in conjunction with a heptanucleotide “slippery site” and an intervening spacer sequence. A comprehensive study of analyzing the sequence signatures and composition of all overlapping gene segments harboring these frameshift elements from four different RNA virus families was carried out. Chapter 4 describes the sequence composition of all overlapping gene segments in Astroviridae, Coronaviridae, Retroviridae and Luteoviridae viral families which are known to employ -1 PRF process for maintaining their protein products. Sequence analysis revealed preference for GC bases in the structure forming sequence regions. A comparative study between multiple sequence alignment and secondary structure prediction revealed that while pseudoknots have a clear preference for specific base-pairs in their stem regions, viral families that employ a hairpin loop as -1 PRF structure, doesn’t show this preference. Information derived from secondary structure prediction was then used for RNA ab initio modeling to generate tertiary structures. Furthermore, the structural parameters were calculated for the helices of the frameshift inducing pseudoknots and were compared with the values calculated for a set of non -1 PRF inducing H-type pseudo-knots. This study highlighted the differences between -1 PRF pseudoknots and other H-type pseudoknot structures as well as specific sequence and structural preferences of the former. Chapter 5 discusses the dynamics of a tRNA transport factor Exportint (Xpot), which transports mature tRNA molecules from nucleus to cytoplasm and belongs to Importitβ family of proteins. The global conformational dynamics of other transport receptors has been reported earlier, using coarse-grained modeling and Elastic Network Models (ENMs), but a detailed description of the dynamics at an all-atomic resolution was lacking. This transport requires association of Xpot with RanGTP, a G-protein, in the nucleus and hydrolysis of RanGTP in the cytoplasm. The chain of events leading to tRNA release from Xpot after RanGTP hydrolysis was not studied previously. With these objectives, several molecular complexes containing Xpot bound to Ran or tRNA or both in the GTP and GDP ligand states as well as free Xpot structures in nuclear and cytosolic forms were studied. A combination of conventional and accelerated molecular dynamics simulations was used to study these molecular complexes. The study highlighted various aspects associated with tRNA release and conformational change which occurs in Xpot in cytosolic form. The nuclear to cytosolic state transition in Xpot could be attributed to large fluctuations in C-terminal region and dynamic hinge-points located between specific HEAT repeats. A secondary role of Xpot in controlling the quality of tRNA transport has been proposed based on multiple sequence and structure alignment with Importin-β protein. The loss of critical contacts like hydrogen bonds and salt bridges between Xpot/Ran and Xpot/tRNA interface was evaluated in order to study the initial effects of RanGTP hydrolysis and how it influences receptor-cargo binding. This study revealed various aspects of tRNA transport process by Xpot, not understood previously. The results presented in this thesis illustrate the role of RNA sequence elements and pseudoknots present in RNA viruses in modulating -1 PRF process and how multiple environmental factors affect -1 PRF inducing ability of the structure. From the studies of Xpot and its complexes, the effects of GTP hydrolysis leading to tRNA dissociation have been presented and the progression of conformational transition in Xpot after tRNA dissociation has been highlighted. Chapter 6 summarizes major conclusions of this thesis work. The refolding of single stranded RNA chains, subjected to a previous unfolding simulation is studied. Appendix A describes this work and initial results. Appendix B describes the effect of improved molecular dynamics force fields, containing corrections for χ torsion angle for RNA, on the conformation of tertiary RNA structures. Part of the work presented in this thesis has been reported in the following publications. 1.Asmita Gupta and Manju Bansal. Local Structural and Environmental Factors De-fine the Efficiency of an RNA Pseudoknot Involved in Programmed Ribosomal Frameshift Process. J. Phys. Chem. B. 118 (41), pp 11905-11920. 2014 2.Asmita Gupta, Senthilkumar Kailasam and Manju Bansal. Insights Into Nucleo-cytoplasmic Transport of tRNA by Exportin-t. Manuscript under review. List of manuscripts that are being prepared from the work reported in Chapter 3 in this thesis. 1 Asmita Gupta and Manju Bansal. The role of sequence effects on altering the un-folding pathway of an RNA pseudoknot: a steered molecular dynamics study. Manuscript in preparation. 2 Asmita Gupta and Manju Bansal. Molecular basis for nucleocytoplasmic transport of tRNA by Exportin-t. Journal of Biomolecular Structure and Dynamics, May;33 Suppl 1:59-60, 2015

Made available in DSpace on 2014-06-12T18:02:03Z (GMT). No. of bitstreams: 2 arquivo4132_1.pdf: 2797653 bytes, checksum: 27180e30e0a15ede81873b5001d528e0 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2008 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Nesta Tese, são investigados dois temas de interesse atual, o transporte de partículas brownianas interagentes e as transições de fase em sistemas magnéticos quânticos. No primeiro, o transporte de partículas brownianas interagentes sujeitas a um potencial de substrato do tipo catraca foi investigado numericamente através da dinâmica de Langevin. Medidas da corrente de partículas, excitadas por uma força externa senoidal, foram analisadas como função da amplitude (A) e frequência (w) da força externa, do número de ocupação dos poços de potencial (n) e do ruído térmico (T). Em temperatura nula no regime adiabático, múltiplas inversões de corrente ocorrem em função de n, devido ao movimento das partículas que ficam menos presas em um potencial efetivo, o qual não preserva a simetria do potencial original devido à influência de uma certa fração de partículas efetivamente presas ao potencial. Observa-se, também, que o aumento da amplitude promove a deslocalização gradual das partículas presas, alterando a simetria do potencial efetivo, induzindo n¡1 oscilações (inversões) da corrente de partículas para um valor de n > 1. No regime de altas temperaturas, inversões de corrente são observadas pela ativação térmica das partículas efetivamente presas ao potencial, restabelecendo a sua simetria original e o movimento na sua direção mais suave. No regime de frequências moderadas, a corrente de partículas apresenta um comportamento discretizado em função da amplitude externa, sendo os intervalos ou degraus de corrente dependentes da densidade de partículas. Por fim, o efeito conjunto de altas temperaturas e altas frequências induz o movimento na direção mais íngreme do potencial, invertendo novamente o sentido da corrente de partículas. No segundo tema, foi investigada a criticalidade da cadeia quântica de spins Ising submetida a campo transverso com interações competitivas diluídas entre segundos vizinhos, em T = 0. O parâmetro k = ¡J2=J1 mede a razão entre os acoplamentos ferromagnéticos entre primeiros vizinhos (J1) e os antiferromagnéticos entre segundos vizinhos (J2), e o parâmetro e mede a diluição (desordem) entre acoplamentos entre segundos vizinhos. O caso e = 0 corivresponde ao modelo Ising puro em campo transverso e o caso e = 1 corresponde ao modelo ANNNI (Axial Next Nearest Neighbor Ising Model) em campo transverso. Ambos possuem a mesma classe de universalidade do modelo Ising clássico bidimensional. Foi investigado através da técnica de Monte Carlo quântico, o efeito da desordem sobre a criticalidade deste sistema. A técnica empregada consiste na combinação de um algoritmo de cluster em tempo imaginário contínuo adaptado para tratar interações competitivas que emprega o formalismo de Suzuki-Trotter que mapeia o sistema quântico d dimensional em um sistema clássico correspondente em d +1 dimensões, com interações anisotrópicas e com a desordem congelada em uma das direções. Foram calculados os expoentes dinâmicos z e o expoente do comprimento de correlação n no regime de competições fracas k = 0:1 em função de e , utilizando-se o comportamento de escala de tamanho finito anisotrópico apropriado para este sistema. Os resultados obtidos indicam uma mudança da criticalidade quântica do sistema induzida pela desordem entre os acoplamentos, revelando que esta é relevante para este sistema. Outro modelo magnético quântico estudado foi o modelo de Heisenberg anisotrópico de spin 1=2, definido na rede hierárquica do tipo diamante com p conexões. Neste caso, foi usada a técnica do grupo de renormalização no espaço real, com fator de escala b=2, dentro da aproximação de Migdal- Kadanoff para sistemas quânticos. Uma relação de recorrência para a magnetização local foi obtida relacionando os valores dos spins internos à rede na geração n com os valores dos spins externos na geração n¡1. Os expoentes críticos b foram calculados nos pontos fixos instáveis do tipo Ising e Heisenberg em função da dimensão fractal da rede

L'objet de cette thèse est l'étude de phénomènes critiques hors-équilibre. Pour décrire ces systèmes, l'utilisation d'équations de Langevin est souvent incontournable car elles permettent une description heuristique relativement simple du phénomène, construite en ajoutant un terme de bruit à la dynamique macroscopique. J'ai montré qu'il est toutefois possible, dans le cas des processus de réaction-diffusion, d'aller au delà de cette approche et de dériver une équation de Langevin exacte qui décrit la dynamique au niveau microscopique. Une seconde partie de ma thèse est consacrée à l'étude de modèles spécifiques de phénomènes critiques hors-équilibre à l'aide du groupe de renormalisation non-perturbatif (NPRG), une version moderne des blocs de spins de Wilson et Kadanoff. À l'équilibre, cet outil tire son succès de sa capacité à contrôler les fluctuations au voisinage de la transition grâce à un régulateur. Hors équilibre, les fluctuations temporelles doivent être traitées de la même façon, et j'ai donc conçu un régulateur qui contrôle à la fois les fluctuations spatiales et temporelles. Enfin, j'ai appliqué le NPRG à un modèle d'érosion. En effet, l'apparition générique de lois d'échelles dans les paysages suggère l'existence d'un mécanisme sous-jacent qui conduit ces systèmes à leur point critique. L'équation de Kardar-Parisi-Zhang modélise l'érosion à grande échelle (>2 km), mais ne s'accorde pas aux observations à plus petite échelle. Un modèle différent, tenant compte de l'anisotropie (la pente d'une montagne), fut donc suggéré. À l'aide du NPRG, je montre que ce modèle possède une ligne de points fixes qui correspond à un domaine continu d'exposants d'échelle. / This manuscript is focused on the study of critical phenomena taking place out-of-equilibrium. In the description of such phenomena, Langevin equations are ubiquitous and are usually derived in a phenomenological way by adding a noise term to a deterministic mean-field equation. However, I show that for reaction-diffusion processes it is in fact possible to derive an exact Langevin equation from the microscopic process. A second part of my thesis work has been devoted to the study of specific nonequilibrium critical phenomena using the nonperturbative renormalization group (NPRG), which is a modern implementation of Wilson and Kadanoff's block-spin idea. This tool, very powerful in an equilibrium context, takes care of the growing spatial fluctuations that arise near criticality through the use of a regulator. In a nonequilibrium context, the temporal fluctuations also have to be controlled. I have therefore designed a regulator that tackles both spatial and temporal fluctuations. Finally, I have applied the NPRG techniques to a model of landscape erosion: indeed, the generic scaling behaviour that appear in erosional landscapes suggests the existence of an underlying mechanism naturally fine-tuned to be critical. The Kardar-Parisi-Zhang equation seems to give a correct model for landscape erosion at large length scale (>2 km), but fails to predict the scaling observed at smaller scale. A different model was thus suggested which takes into account the intrinsic anisotropy at smaller length scale (the slope of the mountain). Using NPRG techniques, I show that this model possesses a line of fixed points associated with a continuous range of scaling exponents.