This master thesis deals with synthesis of 6I -N-monosubstituted β-CD bearing a linear spacer of various lenghts containing disulfidic bond and terminated by amine. Whole series was succesfully prepared by nucleophilic substitution of toluenesulfonyl group on tosyl β-CD by a spacer's amine group. In case of the shortest spacer (cystamine) 35 % yield was achieved. Synthesis of β-CD derivatives using longer and more lipophilic spacer derived from di-, tri- and tetraethylenglycol yielded 66 to 85 %. The oligoethylene spacers were prepared by standard chemical modifications. A separation method using n-butanol elution mixtures was optimized for isolation of β-CD derivatives. To better understand the β-CD derivative behavior in solution, molecular dynamics (MD) computations were used. The synthetized species were intended to be used for fluorescent sensor construction. For the same reason the inclusion of small organic molecules in β-CD cavity was studied with molecular dynamic simulations. MD method for computation of relative binding energy was optimized and gave values of right sign and order of magnitude.

Submitted by Everaldo Pereira (pereira.evera@gmail.com) on 2018-07-03T23:54:04Z No. of bitstreams: 1 Dissertação Mestrado Michelli.pdf: 4172618 bytes, checksum: 5fb3f009f247a36e9b59dcc9021ae983 (MD5) / Approved for entry into archive by NUBIA OLIVEIRA (nubia.marilia@ufba.br) on 2018-07-13T20:25:33Z (GMT) No. of bitstreams: 1 Dissertação Mestrado Michelli.pdf: 4172618 bytes, checksum: 5fb3f009f247a36e9b59dcc9021ae983 (MD5) / Made available in DSpace on 2018-07-13T20:25:34Z (GMT). No. of bitstreams: 1 Dissertação Mestrado Michelli.pdf: 4172618 bytes, checksum: 5fb3f009f247a36e9b59dcc9021ae983 (MD5) / A Sequência Metavulcanossedimentar Igaporã-Licínio de Almeida está inserida na borda leste do Cinturão de Dobramentos e Cavalgamentos do Espinhaço Setentrional, um dos componentes do Corredor do Paramirim, na porção intracontinental do Orógeno Araçuaí. O objetivo principal desse trabalho é entender os processos metalogenéticos que levaram à magnetitização e à hematitização em protominérios estéreis situados em cinturões de dobramentos e cavalgamentos de orógenos intracontinentais. Na área de estudo ocorrem xistos máficos, itabiritos quartzosos, anfibolíticos e carbonáticos e rochas carbonatossilicáticas. Os domínios magnetitizados e hematitizados ricos ocorrem, principalmente, nos itabiritos. A geometria geral do depósito está relacionada com a presença de duplexes compressionais com topo estrutural para SW. Essas são estruturas relacionadas com a Zona de Cisalhamento Carrapato e, como elementos de maior escala contém uma foliação Sn, que é representada por um bandamento composicional e por uma xistosidade paralelizada a ele. A foliação Sn foi observada em todas as escalas e nos itabiritos transpõe uma foliação Sn-1 presente em dobras isoclinais intrafoliais. Estruturas S/C/C’, boudins, pinch –and swell, bem como dobras em bainha e dobras em cortina são coetâneas à formação dessa foliação metamórfica de transposição. Uma lineação de estiramento mineral (Lxn) da mesma fase deformacional integra o arcabouço estrutural, bem como uma incipiente foliação que trunca a Sn- 1//Sn e que se relaciona com as dobras em cortina. A alteração hidrotermal é coetânea com o desenvolvimento das zonas de cisalhamento, tendo sido identificados estágios de potassificação (biotitização e moscovitização), alteração à clorita, carbonatação, alteração a carbonato e formação de óxidos de ferro (magnetita e hematita). A magnetita hipogênica aloja-se em estruturas C’ e em charneiras de dobras isoclinais intrafoliais. Essa geração cresce incluindo silicatos e carbonatos esqueletiformes ou formando bordas de corrosão em: (i) ferri-tschermakita e oligoclásio em xistos máficos; (ii) carbonato, actinolita, quartzo, biotita em rochas carbonatossilicáticas; (iii) quartzo em itabiritos quartzosos; (iv) cumingtonita e quartzo em itabirito anfibolítico; e (v) quartzo, carbonato e moscovita em itabiritos carbonáticos. Além disso, esses óxidos de ferro também substituem moscovita, carbonatos, epidoto e porfiroblastos de anfibólios que truncam a Sn. A hematita é platiforme e ocorre em agregados policristalinos marcando a foliação Sn-1//Sn, bem como a foliação plano axial (Sn) em dobras isoclinais intrafoliais. A sua formação sugere condições de maior oxidação do sistema hidrotermal. Determinações por LA-ICPMS mostram que, de forma geral, nos itabiritos quartzosos e anfibolíticos as magnetitas hipogênicas são mais ricas em Elementos Terras Raras Leves do que as magnetitas precoces e sua composição se aproxima da composição da rocha encaixante da mineralização. A formação de domínios com enriquecimento em hematita e magnetita está relacionada com a percolação de fluidos hidrotermais que dissolveram silicatos, remobilizaram uma primeira geração de magnetita em itabiritos e precipitaram uma segunda geração desse mineral aproveitando estruturas de cisalhamento ediacaranas. / ABSTRACT - The Igaporã-Licínio de Almeida Metavolcano-sedimentary Sequence is located at the eastern border of the Northern Espinhaço Thrust and Fold Belt, one of the components of the Paramirim Corridor, in the intracontinental portion of the Araçuaí Orogen. The main objective of the present study was to understand the metallogenetic processes that lead to the magnetization and hematitization in sterile proto-ores located in thrust and fold belts of intracontinental orogens. Mafic schists, itabirites of quartz, amphibolite and carbonate composition, and carbonate-silicate rocks occur in the study area. Rich magnetized and hematitized domains occur mainly in itabirites. The general geometry of the deposit is related to the presence of compressional duplexes that present their structural top towards SW. These structures are related to the Carrapato Shear Zone and contain as large scale elements Sn foliation, which is represented by compositional banding and parallel schistosity. Sn foliation was observed at all scales and in the itabirites it transposed Sn-1 foliation present in intrafolial isoclinal folds. S/C/C’, boudins, pinch-and-swell structures, as well as sheath and curtain folds are coetaneous with the formation of this metamorphic transposition foliation. Mineral stretching lineation (Lxn) from the same deformational phase integrates the structural framework, as well as an incipient foliation that truncates Sn-1//Sn and is related to curtain folds. Hydrothermal alteration is coetaneous with the development of shear zones, where stages of potassification (biotitization and muscovitization), alteration into chlorite, carbonation, alteration into carbonate, and formation of iron oxides (magnetite and hematite) were identified. Hypogenic magnetite lodges itself in C’ structures and in fold axes of intrafolial isoclinal folds. This generation grows either including silicates and skeletal carbonates or forming corrosion edges in: (i) ferrotschermakite and oligoclase in mafic schists; (ii) carbonate, actinolite, quartz, biotite in carbonate-silicate rocks; (iii) quartz in quartz-rich itabirites; (iv) cummingtonite and quartz in amphibolitic itabirites; and (v) quartz, carbonate, and muscovite in carbonate itabirites. In addition, this iron oxide also replaced muscovite, carbonates, epidote, and are found in porphyroblasts of amphiboles that truncate the Sn foliation. Hematite is platy-shaped and occurs in polycrystalline aggregates, characterizing the Sn-1//Sn foliation, as well as the axial plane foliation (Sn) in intrafolial isoclinal folds. Its formation suggests higher oxidation conditions of the hydrothermal system. The LA-ICPMS technique showed that, in general, in quartz-rich and amphibolitic itabirites, hypogenic magnetites are richer in Light Rare Earth Elements than early magnetites, and their composition is close to that of the country rock of the mineralization process. The formation of hematite- and magnetite-enriched domains is related to the percolation of hydrothermal fluids that dissolved silicates, remobilized the first generation of magnetites in itabirites, and precipitated a second generation of this mineral taking advantage of Ediacaran shear structures.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-01-13T11:03:19Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Alline Torquato Vasconcelos - 2014.pdf: 3499445 bytes, checksum: 93905607504e61e452d7ce82396c17a9 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-01-13T11:04:23Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Alline Torquato Vasconcelos - 2014.pdf: 3499445 bytes, checksum: 93905607504e61e452d7ce82396c17a9 (MD5) / Made available in DSpace on 2015-01-13T11:04:23Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Dissertação - Alline Torquato Vasconcelos - 2014.pdf: 3499445 bytes, checksum: 93905607504e61e452d7ce82396c17a9 (MD5) Previous issue date: 2014-06-06 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Lamivudine (β-L-2',3'-dideoxy-3'-thiacytidine, 3TC) is a nucleoside-based anti-HIV/HBV drug that has provided insights into the nucleic acid double-stranded helix assembly. Two crystal structures thereof assembled with nucleobase pairing and helical stacking as mimicries of DNA, but without the phosphodiester linkages in the fiber periphery, have recently demonstrated that nucleosides bring themselves the chemical information to assemble DNA duplexes even if the covalent backbone is absent. Here, we report the third structural example in which nucleosides are base-paired and helically base-stacked. A DNA-like double stranded helix was prepared cocrystallizing lamivudine with fumaric acid. We have named it as lamivudine duplex III. When substituting maleic acid present in the first example of lamivudine duplex for its trans-stereoisomer, the formation of a DNA-mimicry is still observed but with changes in the crystal stoichiometry, nucleobase pairing pattern and duplex backbone. Lamivudine duplex III exhibits both base pairing motifs present in the antecedent duplexes. In this structure, there are four protonated lamivudine molecules paired in-plane with four neutral ones. These crystallographically independent base pairs are held together through three hydrogen bonds as occurs in lamivudine duplex I made up of cytosine-cytosine+ base pairing only. But, contrarily to the duplex I with pairing between neutral and cationic drug units only, the duplex III has one neutral 3TC=3TC pair in its asymmetric unit. These molecules are kept in contact through only two peripheral N―H•••O hydrogen bonds as in two of the three neutral lamivudine pairs of the second example of lamivudine duplex. In both structures, each neutral pair is face-to-face stacked on top of one another and face-to-tail stacked on bottom of another one. Even in agreement with its higher structural complexity, the duplex III is present with very puckering conformations besides the three different orientations of the OH moiety at C5’. Five-membered oxathiolane ring adopts three envelop puckering modes and two twist conformations. This is the first report of a twist pucker for lamivudine despite of the large number of reported crystal structures thereof. Another remarkable characteristic of the duplex III is in its fiber periphery. There are hydrogen bonds between the 5’-OH moieties of neighbor pairs pointing in the direction of the missing phosphodiester linkages that would covalently bond two adjacent monomers in the strand. Furthermore, the geometry of these interactions reveals the antiparallel orientation of each strand relative to one another into the nucleoside duplex backbone. Noteworthy similarities between the duplexes crystallizing together with either hydrogen maleate or hydrogen fumarate are their left handedness and the outline of surface grooves of similar depth. But, while all hydrogen maleate counterions are lodged on the grooves of the duplex I, some hydrogen fumarate units are also interacting with themselves into one-dimensional chain of counterions. The third example of unusual double-stranded helices of lamivudine strengthens the fact that nucleosides can self-aggregate into DNA-like duplexes even without the covalent phosphodiester linkages in fiber periphery. Besides that, the structure described here adds knowledge on lamivudine versatility to assemble DNA-mimicry in crystals. / A lamivudina (β-L-2',3'-dideoxy-3'-thiacytidine, 3TC) é um fármaco a base de nucleosídeos utilizado para o tratamento de SIDA e Hepatite B. A obtenção de estruturas do tipo dupla hélice de ácidos nucleicos com esse fármaco tem sido alvo de estudo. Recentemente foram reportadas duas estruturas cristalinas mimetizando DNA, formadas por pares de nucleosídeos empacotados em uma dupla hélice, mas sem ligações fosfodiéster na periferia da cadeia. Estas estruturas demonstraram que os nucleosídeos possuem informação química suficiente para a formação de estruturas dessa natureza mesmo com a ausência das ligações covalentes fosfodiéster. Neste trabalho um terceiro exemplo de uma estrutura contendo bases de nuclosídeos pareadas e sobrepostas helicoidalmente, mimetizando DNA, é reportado. Essa modificação cristalina foi preparada através da cocristalização da lamivudina com o ácido fumárico e a estrutura obtida foi denominada duplex III. Com a substituição do ácido maleico, presente no primeiro exemplo de dupla hélice de lamivudina, pelo seu estéreoisômero trans, o ácido fumárico, a formação de uma estrutura mimetizando o DNA também foi observada, porém, com diferenças na estequiometria do cristal, nos padrões de interação do pareamento das bases, assim como no esqueleto da dupla hélice. O pareamento das bases na duplex III de lamivudina possui padrões de interação semelhante a ambas estruturas precedentes. Na duplex III existem quatro pares parcialmente protonados, onde uma lamivudina protonada está pareada com outra neutra. Esse tipo de pareamento se dá através de três ligações de hidrogênio e é semelhante ao pareamento presente na estrutura da duplex I de lamivudina composto apenas por pares do tipo 3TC+≡3TC. Diferentemente da duplex I que possui exclusivamente pares parcialmente protonados, a duplex III possui também um par neutro do tipo 3TC=3TC na sua unidade assimétrica. O pareamento dessas bases é formado apenas por duas ligações de hidrogênio do tipo N―H•••O, semelhante a dois dos três pares neutros que constituem a duplex II de lamivudina. O empacotamento dos pares neutros na duplex III é semelhante ao da duplex II, cada par neutro empacota com uma padrão face a face com o par que o antecede e face a cauda com o par subsequente. Devido à grande complexidade estrutural da duplex III, temos uma maior variação nas conformações assumidas tanto pelo anel oxatiolano quanto pelo fragmento citosinico, assim como nas três orientações adotadas pelo grupo hidroxílico ligado ao carbono C5’. O anel oxatiolano de cinco membros, adota três diferentes conformações do tipo envelope e duas conformações do tipo cambaleante. Apesar de essas serem as primeiras estruturas reportadas com conformações do tipo cambaleante para a lamivudina, esse tipo de conformação é comum para várias outras estruturas cristalinas. Outra característica que merece destaque na estrutura obtida da duplex III está nos padrões de interação presentes na periferia da dupla hélice. Nota-se a presença de ligações de hidrogênio entre os grupos 5’-OH de pares vizinhos, que ocorrem na direção onde as ligações fosfodiéster deveriam existir entre dois monômeros adjacentes. Além disso, a geometria dessas ligações de hidrogênio revelam uma orientação antiparalela de uma fita em relação a outra no esqueleto da duplex. Existem algumas semelhanças notáveis entre as duplexes I e III, cristalizadas com hidrogenomaleato e hidrogenofumarato, como a espiralização a esquerda e o fato de ambas não possuírem diferença entre sulcos principais e secundários, uma vez que todos os sulcos ao longo da cadeia possuem dimensões semelhantes. Porém, todos os contraíons estão acomodados nos sulcos da duplex I, enquanto que na duplex III alguns contraíons interagem entre si formando uma cadeia unidimensional de contraíons. Esse terceiro exemplo de uma estrutura atípica de dupla hélice de lamivudina reforça o fato de que nucleosídeos podem se agregar em estruturas semelhantes a dupla hélice do DNA, mesmo com a ausência das ligações covalentes fosfodiéster. Além disso a estrutura da duplex III adiciona conhecimento quanto a versatilidade da lamivudina em formar estruturas mimetizando DNA em cristais.

Cette thèse s'intéresse à la dynamique des prismes orogéniques à travers l'étude du cas Himalayen. J'ai utilisé une approche pluri-disciplinaire combinant modélisation numérique, cartographie de terrain, analyse structurale et microstructurale, thermochronologie Ar-Ar et détermination des pics de température métamorphique par RSCM (Raman Spectroscopy of Carbonaceous Material).La modélisation numérique m'a permis d'apporter des contraintes sur les paramètres contrôlant la géométrie actuelle de la chaine. A la suite de cette étude, je propose que les variations latérales observées le long de la chaîne Himalayenne soient générées par la combinaison de deux mécanismes : 1) l'advection asynchrone d'une rampe crustale sous le Moyen Pays Himalayen le long de différents segments, qui entraine la présence et le déplacement de la transition topographique le long de la chaîne; 2) des variations dans le contraste rhéologique entre le plateau du Tibet et la croûte continentale Indienne, qui controlent la formation des klippes et influence la largeur de la chaîne.Le travail de terrain a permis d'apporter des données sur une zone jusqu'alors peu documentée de l'Ouest Népalais. Les observations réalisées, ainsi que les analyses effectuées sur les échantillons rapportés de cette campagne de terrain, m'ont amené à proposer une nouvelle coupe géologique pour cette zone. L'existence du “lesser Himalayan Duplex”, jusqu'alors utilisé pour expliquer cette zone, est ainsi discuté ainsi que la géométrie et la signification du “Ramgarh Thrust”.Par ailleurs, un code de modélisation numérique a été développé afin d'étudier les mécanismes thermiques ayant lieu dans la croûte continentale en cours de migmatisation. Ce modèle, appliqué au massif métamorphique de El Oro en Equateur, nous a amené à mettre en évidence l'existence de mécanismes de convection crustale, lors de la migmatisation, dans cette région. Cette étude méthodologiquement proche de celle réalisée sur le prisme orogénique himalayen, apporte des contraintes sur la formation et la dynamique des plateaux continentaux. / This PhD focuses on the dynamics of orogenic wedges using the Himalayas as a case study. I used a multi-disciplinary approach combining numerical modeling, field mapping, structural and microstructural analysis, Ar-Ar thermochronology and metamorphic peak temperature estimation by RSCM (Raman Spectroscopy of Carbonaceous Material) to provide geometrical and timing constraints on the development and evolution of an upper-crustal scale nappe system.Numerical modeling provided the intuition on the parameters that control the current geometry of the belt. According to this study, I propose that along-strike variations observed along the Himalayan Belt are generated by two parallel mechanisms: 1) The asynchronous underthrusting of a crustal ramp beneath the Lesser Hiamalaya, responsible for the presence and displacement of the topographic transition observed along the belt; and 2) variations in the rheological contrast between the Tibetan Plateau and the colliding Indian continental crust, controlling the formation of klippes and the range width.The fieldwork campaign allowed us to bring new data on an area so far poorly documented: the far western Nepal. Field observations as well as analyses performed on samples collected during the field campaign led us to propose a new geological cross section for this area. The existence of the lesser Himalayan duplex, used so far to explain the structure of the belt in the Karnali River area (Western Nepal), is discussed as well as the geometry and tectonic significance of the Ragmarh thrust.In a parallel study, a numerical code has been developed in order to study the thermal behavior of a partially melted continental crust. This model, applied to the El Oro massif in Equator, led us to show the likely presence of crustal convection during partial melting for this area, in the Triassic. This study is similar to the one on the Himalayan orogenic wedge from a methodological point of view and brings new constraints on the formation and kinematics of continental plateau.

In recent years, several interesting biological roles played by RNA have come to light. Apart from their known role in translation of genetic information from DNA to protein, they have been shown to act as enzymes as well as regulators of gene expression. Protein-RNA complexes are involved in regulating cellular processes like cell division, differentiation, growth, cell aging and death. A number of clinically important viruses have RNA as their genetic material. Defective RNA molecules have been linked to a number of human diseases. The ability of RNA to adopt stunningly complex three-dimensional structures aids in diverse functions like catalysis, metabolite sensing and transcriptional control. Several secondary structure motifs are observed in RNA, of which the double-helical RNA motif is ubiquitous and well characterized. Though DNA duplexes have been shown to be present in many polymorphic states, RNA duplexes are believed to exhibit conservatism. Early fibre diffraction analysis on molecular structures of natural and synthetically available oligo- and polynucleotides suggested that the double-helical structures of RNA might exist in two forms: A-form and A′-form. New improved crystallographic methods have contributed to the increased availability of atomic resolution structures of many biologically significant RNA molecules. With the available structural information, it is feasible to try and understand the contribution of the variations at the base pair, base-pair step and backbone torsion angle level to the overall structure of the RNA duplex. Further, the effect of protein binding on RNA structure has not been extensively analysed. These studies have not been investigated in greater detail due to the focus of the research community on understanding conformational changes in proteins when bound to RNA, and due to the lack of a significant number of solved RNA structures in both free and protein-bound state. While studies on the conformation of the DNA double-helical stem have moved beyond the dinucleotide step into tri-, tetra-, hexa- and octanucleotide levels, similar knowledge for RNA even at the dinucleotide step level is lacking. In this thesis, the results of detailed analyses to understand the contribution of the base sequence towards RNA conformational variability as well as the structural changes incurred upon protein binding are reported. Objectives The primary objective of this thesis is to understand the following through detailed analyses of all available high-resolution crystal structures of RNA. 1 Exploring sequence-dependent variations exhibited by dinucleotide steps formed by Watson-Crick (WC) base pairs in RNA duplexes. 2 Identifying sequence-dependent variations exhibited by dinucleotide steps containing non-Watson-Crick (NWC) base pairs in RNA duplexes. 3 Developing a web application for the generation of sequence-dependent non-uniform nucleic acid structures. 4 Investigating the relationship between base sequence and backbone torsion-angle preferences in RNA double helices followed by molecular dynamics simulation using various force fields, to check their ability to reproduce the above experimental findings. Chapter 1 gives an overview of the structural features and polymorphic states of RNA duplexes and the present understanding of the structural architecture of RNA, thereby laying the background to the studies carried out subsequently. The chapter also gives a brief description on the methodologies applied. Relevant methodologies and protocols are dealt with in detail in the respective chapters. Sequence-dependent base-pair step geometries in RNA duplexes A complete understanding of the conformational variability seen in duplex RNA molecules at the dinucleotide step level can aid in the understanding of their function. This work was carried out to derive geometric information using a non-redundant RNA crystal structure dataset and to understand the conformational features (base pair and base-pair step parameters) involving all Watson-Crick (WC) (Chapter 2) and non-Watson-Crick (NWC) base pairs (Chapter 3). The sequence-dependent variations exhibited by the base-pair steps in RNA duplexes are elaborated. Further, potential non-canonical hydrogen bond interactions in the steps are identified and their relationship with dinucleotide step geometry is discussed. Comparison of the features of dinucleotide steps between free and protein-bound RNA datasets suggest variations at the base-pair step level on protein binding, which are more pronounced in non-Watson-Crick base pair containing steps. Chapter 4 describes a web-server NUCGEN-Plus, developed for building and regeneration of curved and non-uniform DNA and RNA duplexes. The main algorithm is a modification of our earlier program NUCGEN that worked mainly for DNA. The WC step parameters and intra-base parameters for RNA were obtained from the work detailed in Chapter 2. The FORTRAN code and input sequence file format was modified. The program has two modules: a) Using the model-building module, the program can build duplex structures for a given input DNA/RNA sequence. Options are available for selecting various derived or user specified base-pair step parameters, and fibre diffraction parameters that can be used in the building process. The program can generate double-helical structures up to 2000 nucleotides in length. In addition, the program can calculate the curvature of the generated duplex at defined length scale. b) Using the regeneration module, double-helical structures of nucleic acids can be rebuilt from the existing solved structures. Further, variants of an existing structure can be generated by varying the input geometric parameters. The web-server has a user-friendly interface and is freely available in the public domain at: http://nucleix.mbu.iisc.ernet.in/nucgenplus/index.html Sequence dependence of backbone torsion angle conformers in RNA duplexes RNA molecules consist of covalently linked nucleotide units. Each of these units has six rigid torsional degrees of freedom (α, β, γ, δ, ε, and ζ) for the backbone and one (χ) around the glycosidic bond connecting the base to the ribose, thereby providing conformational flexibility. An understanding of the relationship between base sequence and structural variations along the backbone can help deduce the rationale for sequence conservation and also their functional importance. Chapter 5 describes in detail the torsion angle-dependent variations seen in dinucleotide steps of RNA duplex. A non-redundant, high resolution (≤2.5Å) crystal structure dataset was created. Base-specific preferences for the backbone and glycosidic torsion angles were observed. Non-A-form torsion angle conformers were found to have a greater prevalence in protein-bound duplexes. Further validation of the above observation was performed by analysing the RNA backbone conformers and the effect of protein binding, in the crystal structure of E. coli 70S ribosome. Chapter 5 further describes the molecular dynamics simulation studies carried out to understand the effect of force fields on the RNA backbone conformer preferences. A 33mer long duplex was simulated using seven different force fields available in AMBER and CHARMM program, each for 100 ns. Trajectory analyses suggest the presence of sequence-dependent torsion angle preferences. Torsion angle conformer distribution closer to that of crystal structures was observed in the system simulated using parmbsc0 force field. Molecular dynamics simulation studies of AU/AU base-pair step A unique geometric feature, unlike that in other purine-pyrimidine (RY) steps in the crystal dataset analysis, was reported for AU/AU step (see Chapter 2). Appendix 1 describes the work carried out to validate these features observed in the crystal structures using simulation studies. Additionally, the effect of nearest-neighbor base pairs on the AU/AU step geometry were examined. General Conclusion Overall, the findings of this thesis work suggest that RNA duplexes exhibit sequence-dependent structural variations and sample a large volume of the double-helical conformational space. Further, protein binding affects the local base-pair step geometry and backbone conformation.