Dissertations / Theses on the topic 'Conformation'
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Ferrari, Marta. "Dynamic conformation : the influence of conformation on equine locomotion." Thesis, Royal Veterinary College (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.519518.
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Querolle, Olivier. "Synthèse des taxoïdes à conformation bloquée : vers la conformation active du docetaxel." Paris 11, 2002. http://www.theses.fr/2002PA114831.
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Hogg, John Kirtley. "Conformation of metal chelates." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259482.
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Link, Justin J. "Ultrafast Protein Conformation Dynamics." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1230584570.
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Viriyasuthee, Chatavut. "Problem solving by spatial conformation." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107862.
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In computational complexity theory, a reduction is an approach to solving one problemby transforming it into another reference problem in which a solution already exists,thus providing the solution to the original problem in an efficient manner especiallywhen compared with solving the problem directly, which can be costly or even infeasible.The concept of reduction is not only limited to theory; in practice, humansuse past experience to solve problems by \emph{conforming} them, based on analogical reasoning, to known ones that are contained in references or memories.However, because the information retained in references is not always accurate and sometimes filled with redundancies or missing details, the conformation must somehow be robust enough to tolerate these uncertainties.In this thesis, we construct a framework for problem solving by reduction, and we present it in the robotics domain where contexts of problems can be represented using graphical spaces. The process has to match an input problem space to another one in a reference in order to retrieve a solution; we call this process spatial conformation. The content of this thesis can be divided into two parts.First, we develop a general approach and mathematical framework for a range of problem solving challenges to be addressed by reduction. Then we shift our attention to a class of constraint satisfaction problems formulated within the spatial conformation framework. An implementation for each part in robotics applications has been demonstrated to serve as empirical evaluation.Selon la théorie de la complexité des algorithmes, une réduction est une approche pour résoudre unproblème en le transformant en un autre problème de référence qui a déjà été résolu. Ceci permet de trouver une solution à ce problème initial d'une manière efficace, comparemment à essayer de le résoudre directement, ce qui pourrait être coûteux ou même infaisable. Le concept de réduction n'est pas seulement constrainte à la théorie, en pratique,les humains utilisent leurs expériences pour résoudre de nouveaux problèmes en se basant surleurs raisonnements analogiques et en les conformant aux problémes qui se trouvent dans leurs références ou leurs souvenirs. Cependant, parce que les informations conservées dans les références ne sont pas toujours exactes etparfois manquent des détails, la conformation doit en quelque sorte être suffisamment robuste pour tolérer ces incertitudes. Dans cette thèse, nous construisons un systéme de résolution de problèmes basé sur la méthode de réduction, et nous le présentons dans le domaine de la robotique dans lequel les contextes des problèmes peuvent être représentés dans une espace geométrique. Nous définissons la conformation spatiale par le processus de correspondence entre un probléme d'origine et un autre probléme de référence. Tout d'abord, nous développons une approche générale pour résoudre une série de problèmes devant être traités par réduction. Par la suite, nous mettons l'accent sur une catégorie de problèmes de satisfaction de constraintesformulé dans le système de conformation spatiale. Une implémentation de chaque partie dans les applications de la robotique a été démontrée pour servir d'évaluation empirique.
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Lu, Yanling. "Solution conformation of engineered antibodies." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442304.
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Oussaid, Boualem. "Thiophène, pyrrole : synthèse, conformation, macrocycles." Toulouse 3, 1992. http://www.theses.fr/1992TOU30198.
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De nouveaux composes, derives du thiophene ou du pyrrole ont ete synthetises en plusieurs etapes. La conformation de divers composes thiopheniques ou pyrroliques a ete etablie a partir de calculs theoriques, de mesures de moments dipolaires et a partir du couplage stereospecifique a travers cinq liaisons. Quelques macrocycles possedant deux, trois ou quatre restes thiophene ou pyrrole a 18, 20, 30, 34 ou 40 chainons ont ete obtenus par des cyclisations de type 2+2, 3+3 ou 4+4
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Bowers, David J. "Chlorophosphazenes: Synthesis, Structure and Conformation." University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1374508951.
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Albiser, Guy. "Etude des conformations et des transitions de forme de l'ADN et des polynucléotides par la diffraction RX de fibres et la modélisation moléculaire." Nancy 1, 1992. http://docnum.univ-lorraine.fr/public/SCD_T_1992_0017_ALBISER.pdf.
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L'ADN et les polynucleotides étirés en fibres orientées sont étudiés par diffraction des rayons X de conditions physico-chimiques modifiables: l'humidité relative environnante, le pourcentage du cation alcalin associé, la fixation de cation métallique et la tension mécanique appliquée. En utilisant les informations obtenues par diffraction RX et des contraintes structurales provenant de résultats spectroscopiques, il est proposé: une discrimination entre modèles conformationnels de la forme b; des modèles conformationnels pour les formes a, b, c de l'ADN et d du poly (da-dt)#2. Une méthode originale, fondée sur les mesures de dimension de fibre, permet d'analyser les transitions a-b et b-c de l'ADN, d- a-b, d-b du poly (da-dt)#2 et z-b du poly (dc-dc)#2. Pour chaque transition, on mesure les variations du nombre de molécules d'eau associées à un nucléotide.
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Florane, H. "Exploring protein conformation with mass spectrometry." Thesis, University of Edinburgh, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.650980.
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The first part of this thesis describes the development and viability of a phase I screening system for obtaining a rank order of affinity of novel ligands against the immunophilin, Cyclophilin A (CypA). The naturally occurring inhibitor Cyclosporin A (CsA) was used as a positive control to validate a method for calculating the dissociation constant (Kd). An HPLC autosampler and pumping system was used as a high throughput on-line electrospray ionisation (ESI)-MS sampling system. Optimised ESI conditions were then used to screen novel ligands from 3 combinatorial libraries and approaches for data analysis is discussed. Hydrogen/deuterium exchange (HDX) can be used directly and indirectly as a means for studying protein conformations. Melittin, the major component of honey bee venom is taken here as a model system for studying secondary structure in solution and the gas phase. Comprising a 26 amino acid polypeptide, melittin occupies a random coil in aqueous conditions which can be transformed into an α-helix under increasingly hydrophobic conditions. A variety of HDX techniques were utilised: i) comparing rats of deuterium (d-) uptake by direct infusion – ESI at different pDs and methanol concentrations; ii) PLIMSTEX (protein-ligand interactions by mass spectrometry, titration and HDX) at high and low salt concentrations with varying pDs; iii) gas phase exchange in an LCQ ion trap using He/d-methanol as the bath gas. Melittin was pre-incubated in a variety of methanol concentrations. Comparing results from these different approaches, α-helical retention has been shown to exist in the N-terminal half of the peptide. All the afore-mentioned techniques developed using melittin were adapted for CypA. Comparisons of d-uptake in the presence and absence of CsA shows the ligand to have a stabilising affect on the protein.
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Hodgson, Michael Keith. "Studies of DNA conformation and interaction." Thesis, University of York, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323536.
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Foster, Timothy John. "Conformation and properties of xanthan variants." Thesis, Cranfield University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333983.
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Teo, Chuan-Tze. "Conformation and reactivity in molecular modelling." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615977.
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Raussens, Vincent. "Lipid-bound conformation of exchangeable apolipoproteins." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210774.
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zhao, lei. "Conformation and chirality in liquid crystals." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1532846139067875.
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Naidoo, Dhesigen P. "Metals and the conformation of fibrin." Master's thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/26555.
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The carboxy terminal of the γ-chain of human fibrinogen contains at least three biologically. important functional domains: (i) the fibrinogen γ-chain polymerisation centre, (ii) the platelet receptor domain and (iii) the site for staphyloccocal clumping. The nature of the site specificity of these interactions necessitates the existence of a preferred conformation for this region, the nature of which has yet to be clearly established. A novel zinc metalloproteinase isolated from puff adder venom (PAV protease) capable of specifically cleaving the di-γ-chain of transglutaminase (Factor XIIIa) catalysed crosslinked plasmin derived D-dimer into apparently symmetrical monomers has been described. The activity is fibrin specific and displays an unusual site specificity for the γ-carboxy terminal domains within the crosslink region. The activity was reported to be potentiated by zinc. The effect of zinc on the digestion of D-dimer by PAV protease was evaluated by SDS-PAGE and by a fluorimetric technique utilising a fluorescent dansylcadaverine conjugate of the substrate (f-D-dimer). A differential zinc binding study determined that the potentiation of activity by zinc was due to a zinc-substrate rather than a zinc-enzyme interaction. The binding constant for zinc to D-dimer was determined by Scatchard analysis of zinc titration data. The interaction of zinc and f-D-dimer was confirmed by fluorescence anisotropy determinations. The nature of the coordination capsule around the metal cation was determined by examining a cobalt-fibrin-D-dimer complex and characterising the difference visible absorption spectrum thereof. The donor ligands from the D-dimer fragment for the metal ion were determined as histidines by examining zinc(II) and cobalt(II) binding to diethylpyrocarbonate modified fibrin-D-dimer and hydroxylamine treated DEPC-fibrin-D-dimer. Through this study it has been established that the PAV protease cleavage of the di-γ-chain of the plasmin derived D-dimer fragment is potentiated by zinc(II) ions through the formation of a novel zinc determined conformation of fibrin-D-dimer. This presents the possibility of a fibrinspecific neo-epitope being manifested in the presence of zinc ions that could provide a means to determine fibrin degradation products more specifically. A model for the neo-epitope has been proposed.
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Nicholls, Robert Adam. "Conformation-independent comparison of protein structures." Thesis, University of York, 2011. http://etheses.whiterose.ac.uk/2120/.
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The comparative analysis of protein structures is often performed in order to identify and explore similarities/dissimilarities present between target structures. Whilst many tools are available for structural comparison, the development of new tools providing different information is desirable. The work presented here concerns the development of ProSMART (Procrustes Structural Matching Alignment and Restraints Tool), a tool to aid the comparative analysis of protein structures. Primarily, the software is used for conformation-independent pairwise structural alignment, allowing identification of local similarities, and quantification of dissimilarities. Functionality also allows the identification and superposition of rigid substructures, providing output that allows visualisation of local dissimilarities by means of residue-based scoring. The ProSMART pairwise alignment method optimises the net agreement of local structures along the chain, using structural fragments. In order to maintain conformation-independence, the structure-based residue alignment does not enforce global rigidity of chains, nor domains. This feature makes the tool suited to the analysis of domain movement and other conformational changes, as well as for the identification of structural units conserved between seemingly different structures. Given an alignment, ProSMART can be used to generate external restraints on the distances between relatively close atoms, for use in the crystallographic refinement of macromolecules. Using one or more similar structures, the software generates restraints that are intended to help the target protein adopt a conformation that is more reasonable, whilst allowing global flexibility. Such restraints may stabilise refinement in some cases, especially at low resolution where experimental data alone may not be sufficient. We also present a method of Procrustes score normalisation, which allows the consideration of the significance of observed fragment scores. It is suggested that the resulting global scores for the overall pairwise agreement of protein structures may provide an interesting new way of viewing protein fold space.
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Héliou, Amélie. "Molecular conformations and game theory." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLX033/document.
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Les protéines et acides ribonucléiques sont les principaux acteurs de nombreux processus cellulaires.Comprendre leurs fonctions, structures et interactions est un challenge important.Les méthodes expérimentales fournissent des informations sur la structure et la dynamique des molécules.Cependant les méthodes expérimentales sont limitées par le nombre de molécules qu'elles peuvent observer et les moyens qu'elles requièrent.Les méthodes de prédiction permettent d'obtenir des informations structurelles de façon quasi-automatique.Pour s'assurer de leur fiabilité, elles sont testées sur des données expérimentales.Nous présentons une procédure basée sur la cinétique inverse pour trouver une transition entre deux conformations d'un ARN tout en conservant sa structure secondaire.Nous obtenons des résultats comparables à l'état de l'art, ce qui montre que notre sélection des degrés de liberté est pertinente.De plus, nous utilisons des données partielles, ce qui permet d'utiliser différents types de résultats expérimentaux.Nous abordons aussi le problème du repliement protéique par une approche de théorie des jeux.Nous représentons une protéine par un jeu où les joueurs sont les acides aminés et les stratégies, les angles dièdres.La prédiction de structure peut alors être vue comme la recherche d'un équilibre dans un jeu multi-joueur où les fonctions d'utilité correspondent à la qualité du repliement.Nous montrons que l'algorithme de non-regret, appelé Hedge, garantit l'élimination des stratégies dominées et la convergence locale vers un équilibre de Nash.Puis, en limitant notre analyse aux jeux de potentiel, nous montrons qu'une classe plus large d'algorithmes, les algorithmes de régularisation, convergent vers un équilibre de Nash presque surementProteins and Ribonucleic Acids are the workhorses of many cellular processes.Understanding their functions, structures and interactions is an important challenge.Experimental methods provide actual information on structure and dynamics of molecules.However they have limitations : they cannot be applied to all molecules, and they need a lot of resources.Prediction methods are almost automatic ways of obtaining structural information.They are tested on experimental data to attest their reliability.We present, here, approaches tackling different problems.We develop a kinematics-based procedure to morph a RNA molecule between conformations while preserving its secondary structure.We obtain results comparable to state of the art methods showing that our selection of degrees of freedom is efficient.Furthermore we only use sparse information allowing for various kinds of experimental inputs.We also look at the protein structure prediction problem from a game theory angle.We represent the protein dynamics as a game, in which players are amino acids and strategies are dihedrals angles.The structure prediction can thus be seen as finding equilibrium in a multi-players game where all players have utility functions corresponding to the quality of the protein structure.We showed that a well-known no-regret algorithm, called Hedge, guarantees dominated strategies to vanish and a local convergence toward Nash equilibria.Furthermore restricting our analysis to potential games we showed that dual-averaging regularized learning algorithms converge toward a Nash equilibrium almost surely
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Hocht, Iris von der. "Fluorescence spectroscopy of recoverin function and conformation." Jülich Forschungszentrum, Zentralbibliothek, 2008. http://d-nb.info/1000288463/34.
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Sehlin, Dag. "Aβ Conformation Dependent Antibodies and Alzheimer's Disease." Doctoral thesis, Uppsala universitet, Geriatrik, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-132736.
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Soluble intermediates of the amyloid-β (Aβ) aggregation process are suggested to play a central role in the pathogenesis of Alzheimer’s disease (AD) by causing synaptic dysfunction and neuronal loss. In this thesis, soluble Aβ aggregates have been studied with a particular focus on the Aβ protofibril, which has served as the antigen for developing conformation dependent monoclonal antibodies. Antibodies generated from mice immunized with Aβ protofibrils were characterized regarding Aβ binding properties and the amino acid sequences of their antigen binding sites. A conformation dependent IgG antibody, mAb158, was further characterized and found to bind to Aβ protofibrils with a 200-fold higher affinity than to monomeric Aβ without affinity for soluble amyloid-β precursor protein (AβPP) or other amyloidogenic proteins. A sandwich enzyme-linked immunosorbent assay (ELISA) based on mAb158 was used to measure soluble Aβ protofibrils in brain extracts from AβPP-transgenic mice. Low levels of protofibrils could also be detected in human AD brain. However, positive signals generated from measurements in AD and control CSF samples were attributed to interference from heterophilic antibodies (HA), generating false positive signals by cross-binding the assay antibodies; consequently, a study on HA interference in Aβ oligomer ELISAs was initiated. A large set of plasma and CSF samples from AD and non-AD subjects were analyzed with and without measures taken to block HA interference, revealing that virtually all signals above the assay limit of detection were false and generated by HA interference. Many types of soluble Aβ aggregates have been described and suggested to impair neuron and synapse function. To investigate the soluble Aβ pool, synthetic Aβ and brain extracts from AβPP-transgenic mice and AD patients were ultracentrifuged on a density gradient to separate Aβ by size under native conditions. Four distinct gradient fractions were defined based on the appearance of synthetic Aβ in atomic force microscopy (AFM) and immunoreactivity in our protofibril specific sandwich ELISA. Interestingly, most Aβ from AD patients and AβPP-transgenic mice separated in the same fraction as toxic synthetic protofibrils.
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Blancafort, Pilar. "Making conformation-specific RNA-binding zinc fingers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0023/NQ47598.pdf.
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Powell, Lynn M. "Conformation and stability of #alpha#-1-antitrypsin." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304646.
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Ingate, Simon Thomas. "Conformation and reactivity of 1,3-heterocyclic systems." Thesis, University of Portsmouth, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304065.
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Perevedentsev, Aleksandr. "Chain conformation and the photophysics of polyfluorenes." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/25742.
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Conjugated polymers may combine the optical and electronic properties of semiconductors with the desirable mechanical and processing capabilities that characterise polymeric “plastic” materials. The first demonstration of electroluminescence from conjugated-polymer-based devices 25 years ago created the field of Plastic Electronics which has since witnessed spectacular scientific and technological progress, yielding novel devices for applications in light-emitting diodes, photovoltaics, electronics, photonics, sensing, and many others. The molecular nature of conjugated polymers results in weak, typically van der Waals-type, interchain bonding which enables straightforward and cost-effective processing of these materials from the melt or solutions. However, the trade-off for this desirable characteristic is that the solid-state microstructure of conjugated polymers can be extremely sensitive to processing conditions, leading to a wide variety of structural polymorphs that limit reproducibility of the optoelectronic properties of devices and, hence, prevent their commercialisation. For this reason small organic molecules are often used in preference to conjugated polymers, since the former’s microstructure can be more precisely controlled via chemical synthesis and deposition protocols. Nevertheless, there are examples of conjugated polymers that also exhibit well-defined structures. This has been demonstrated, among others, for poly(9,9-dioctylfluorene) (PFO) – a widely-studied blue-emitting conjugated polymer – which can adopt a precisely-defined planar-zigzag chain conformation termed the “β-phase”. Introducing a fraction of β-phase chain segments leads to dramatic – and often advantageous – changes to the optoelectronic properties of PFO. In order to harness the β-phase chain conformation of PFO with the aim of optimising its solid-state optoelectronic properties, three distinct directions need to be investigated, which motivated the research presented in this thesis. First, the mechanism responsible for the formation of the β-phase of PFO is still little-understood; specifically, the role of inter-chain interactions in the formation of intra-chain (conformational) order remains ambiguous. To this end, the formation of the β-phase in PFO solutions with common organic solvents was systematically investigated. Unexpectedly, it is found that solution-crystallisation of PFO proceeds via polymer-solvent compound formation, enabled by adoption of the β-phase conformation which features along-chain cavities that allow for simultaneous inclusion/intercalation of solvent molecules of matching volume. Remarkably, it is shown that the physically-bound intercalated solvent stabilises the β-phase conformation in the absence of specific inter-chain interactions. This makes the β-phase conformation distinct from other conformational isomers and crystalline forms of PFO. An additional consequence of β-phase formation by complexation with the solvent is that the β-phase chain conformation is inherently well-defined and crystallisation-condition-invariant in terms of its intermonomer torsion angle. Second, while selected aspects of the influence of the β-phase on the optoelectronic properties of PFO have been reported, many of them deserve further study. For instance, the effect of the relative fraction of β-phase chain segments on absorption and photoluminescence spectra, as well as photoluminescence quantum efficiency (PLQE), is examined. It is demonstrated that, in comparison to the in-plane isotropic, “glassy” films, PLQE is enhanced by up to 15% for a narrow range (7–9%) of β-phase fractions, introduced by film immersion in solvent-nonsolvent mixtures. Furthermore, analysis of dilute (≤ 1 wt % PFO) oriented blends of PFO with polyethylene shows that the β-phase conformation is metastable in the absence of solvent and, therefore, cannot be oriented by tensile drawing. Consequently, retaining a fraction of β-phase chain segments in tensile-drawn PFO-polyethylene blends leads to strong photoluminescence (PL) depolarisation which limits the resulting optical anisotropy. Third, the ability to locally generate the β-phase conformation on sub-micrometre scale in glassy PFO thin films, which is of interest for fabricating a range of photonic structures, has so far presented a challenge from both the structuring and the imaging perspective. A novel form of dip-pen nanolithography is shown herein to provide an effective means of spatial patterning of the β-phase conformation on length scales ≤ 500 nm while retaining the planar format of the film. The accompanying increase in refractive index associated with the adoption of the β-phase conformation can enable a variety of visible-wavelength, conjugated polymer photonic elements, two of which are modelled using complex photonic dispersion calculations. With regard to imaging of the β-phase patterns, spectroscopic Raman mapping is shown to provide a useful alternative to confocal PL microscopy, with an additional advantage of being able to estimate the relative fraction of β-phase chain segments in the patterns. The research presented in this thesis explore the chain conformation of PFO, specifically its β-phase conformational isomer, as an additional parameter space within which its optoelectronic properties can be tailored for optimal device performance. Further improvements to the resolution of dip-pen nanolithography-based spatial patterning of the β-phase may offer the prospect of a versatile approach to visible-wavelength “conformational” metamaterials. The reported molecular PFO compounds can more generally be formed with the organic solvent replaced by a small molecule of desired optoelectronic properties, thereby allowing the fabrication of ultra-regular molecular-level blends comprising a PFO host and a small-molecular guest. A judicious choice of guest molecule might therefore enable new functionalities in PFO-based devices.
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Zhang, Lyndon N. (Lyndon Nuoxi). "Conformation and dynamics of the mammalian chromosome." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/103441.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Biology, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 29-30).
The control of transcription represents a fundamental, initial mechanism by which the regulation of gene expression is implemented. However, while much research has been done on the biochemistry and cellular function of transcription, comparatively little is known on the dynamics of transcriptional mechanisms, their impact on chromatin structure, and concomitant functional consequences. Employing chromatin immunoprecipitation measurements, we report progress towards this goal. We characterize the ensemble chromosome conformation in mouse embryonic stem cells, by measuring interaction, or contact, probabilities between distal genomic loci. We map and describe chromosome loops, consisting of two interacting CTCF sites co-bound by cohesin, that maintain the expression of genes known to promote cell identity, and restrict the expression of genes specifying repressed developmental lineages.
by Lyndon N. Zhang.
S.M.
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Brotherson, Brett Andrew. "Site blocking effects on adsorbed polyacrylamide conformation." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/26509.
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Thesis (Ph.D)--Chemical Engineering, Georgia Institute of Technology, 2008.Committee Chair: Yulin Deng; Committee Co-Chair: Peter Ludovice; Committee Member: James Frederick; Committee Member: Lawrence Bottomley; Committee Member: Preet Singh. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Billsten, Peter. "Studies on the conformation of adsorbed proteins." Lund : Göteborg University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/39776983.html.
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Mancinelli, Michele <1981>. "Conformation and Stereodynamic of Hindered Aromatic System." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1344/2/michele_mancinelli_tesi.pdf.
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The preparation of conformationally hindered molecules and their study by DNMR and computational methods are my thesis’s core.
In the first chapter, the conformations and the stereodynamics of symmetrically ortho-disubstituted aryl carbinols and aryl ethers are described.
In the second chapter, the structures of axially chiral atropisomers of hindered biphenyl carbinols are studied.
In the third chapter, the steric barriers and the -barrier of 1,8-di-aylbiphenylenes are determined.
Interesting atropisomers are found in the cases of arylanthrones, arylanthraquinones and arylanthracenes and are reported in the fourth chapter.
By the combined use of dynamic NMR, ECD spectroscopy and DFT computations, the conformations and the absolute configurations of 2-Naphthylalkylsulfoxides are studied in the fifth chapter.
In the last chapter, a new synthetic route to ,’-arylated secondary or tertiary alcohols by lithiated O-benzyl-carbamates carrying an N-aryl substituent and DFT calculations to determinate the cyclic intermediate are reported. This work was done in the research group of Prof. Jonathan Clayden, at the University of Manchester.
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Mancinelli, Michele <1981>. "Conformation and Stereodynamic of Hindered Aromatic System." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1344/.
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The preparation of conformationally hindered molecules and their study by DNMR and computational methods are my thesis’s core.
In the first chapter, the conformations and the stereodynamics of symmetrically ortho-disubstituted aryl carbinols and aryl ethers are described.
In the second chapter, the structures of axially chiral atropisomers of hindered biphenyl carbinols are studied.
In the third chapter, the steric barriers and the -barrier of 1,8-di-aylbiphenylenes are determined.
Interesting atropisomers are found in the cases of arylanthrones, arylanthraquinones and arylanthracenes and are reported in the fourth chapter.
By the combined use of dynamic NMR, ECD spectroscopy and DFT computations, the conformations and the absolute configurations of 2-Naphthylalkylsulfoxides are studied in the fifth chapter.
In the last chapter, a new synthetic route to ,’-arylated secondary or tertiary alcohols by lithiated O-benzyl-carbamates carrying an N-aryl substituent and DFT calculations to determinate the cyclic intermediate are reported. This work was done in the research group of Prof. Jonathan Clayden, at the University of Manchester.
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COQUARD, REGIS JEAN-MARIE. "La radiotherapie de conformation : acquis et perspectives." Lyon 1, 1994. http://www.theses.fr/1994LYO1M108.
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Hosia, Waltteri. "Molecular mechanisms in amyloid fibril formation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-976-5.
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Rashid, Mahmood Abdur. "Heuristic Based Search for Protein Structure Prediction." Thesis, Griffith University, 2014. http://hdl.handle.net/10072/367134.
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Proteins that are essentially sequences of amino acids, adopt specific folded 3-dimensional (3D) structures to perform their specific tasks. However, misfolded proteins cause fatal diseases. Hence, protein structure prediction (PSP) has emerged as an important multi-disciplinary research problem.
Given a protein sequence, the PSP problem is to find a 3D structure of the protein such that the total free energy amongst the amino acids in the sequence is minimised. In-vitro laboratory methods are time-consuming, expensive, and failure-prone. Conversely, computational methods are NP-hard even when the models are simplified by using low-resolution energy functions and lattice-based structures.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Integrated and Intelligent Systems
Science, Environment, Engineering and Technology
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Bathe, Mark 1975. "Inverse Monte Carlo simulation of biomolecular conformation and coarse-grained molecular modeling of chondroitin sulfate conformation, titration, and osmotic pressure." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/30327.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2004.Includes bibliographical references.
The first part of this thesis is concerned with the solution structure determination problem. Whereas many biomacromolecules, such as proteins, can be adequately characterized by a single conformation in solution, numerous other important molecules (e.g., nucleic acids, carbohydrates, and polypeptides) exhibit conformational isomerism and disorder. For these molecules, the term "structure" does not correspond to a single conformation but rather to an ensemble of conformations. Given a molecular model and experimental data, the goal of the structure determination problem is to solve for an ensemble of conformations that is consistent with the data. Traditional computational procedures such as simulated annealing, however, are not guaranteed to generate a unique ensemble. The computed ensemble is often simply dependent on the user-specific protocol employed to generate it. As an alternative, a numerical method for determining the conformational structure of macromolecules is developed and applied to idealized biomacromolecules in solution. The procedure generates unique, maximum entropy conformational ensembles that reproduce thermodynamic properties of the macromolecule (mean energy and heat capacity) in addition to the target experimental data. As an evaluation of its utility in structure determination, the method is applied to a homopolymer and a heteropolymer model of a three-helix bundle protein. It is demonstrated that the procedure performs successfully at various thermodynamic state points, including the ordered globule, disordered globule, and random coil states. In the second part of this thesis, a molecular model is developed and used to investigate the properties of anionic glycosaminoglycan (GAG) molecules. GAGs are critically important to the structure and biomechanical properties of articular cartilage, an avascular tissue that provides a low-friction, protective lining to the ends of contacting bones during join locomotion.
(cont.) The tissue consists predominantly of two types of macromolecules, collagen and aggrecan. Aggrecan consists of a linear protein backbone with a high mass fraction of covalently attached chondroitin sulfate (CS) GAGs, which endow cartilage with its high compressive modulus via osmotic action. During the onset and progression of osteoarthritis, a debilitating joint disease that affects millions in the US alone, the chemical composition of CS (sulfate type, sulfate pattern, and molecular weight) changes, concomitantly with alterations in the biomechanical properties of cartilage. For this reason, it is of primary biological interest to understand the effects of CS chemical composition on its conformation, titration behavior, and osmotic pressure. To enable the investigation of these properties, a coarse-grained model of CS is developed. Systematically derived from an all-atom description, the model enables the atomistic- based simulation of large-scale macromolecular assemblies relevant to cartilage biomechanics. Extensive comparison with experimental data demonstrates that this computationally efficient model is also quantitatively predictive, despite the absence of any adjustable parameters. 4-sulfation of CS is found to significantly increase the intrinsic stiffness of CS, as measured by the characteristic ratio and persistence length in the limit of high ionic strength. Average sulfate density is found to increase CS stiffness at finite ionic strength due to electrostatic interactions that tend to stiffen the chain backbone. Sulfation type and pattern (the statistical distribution of sulfates along a CS chain) are not found to influence the osmotic pressure, which is found to be sensitive primarily to the mean volumetric fixed charge density.
by Mark Bathe.
Ph.D.
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Gouvion, Catherine. "Etude de la conformation des oligogalacturonides par résonance magnétique nucléaire et modélisation nucléaire." Grenoble 1, 1993. http://www.theses.fr/1993GRE10025.
Full textAbstract:
Une etude conformationnelle de quelques oligogalacturonides, de dp2 a 4, obtenus par hydrolyse enzymatique et chromatographie, a ete entreprise par resonance magnetique nucleaire et modelisation moleculaire. Les parametres rmn mesures en solution (constantes de couplage carbone-proton et effets overhauser nucleaires) peuvent etre convertis en parametres geometriques caracteristiques d'une conformation virtuelle moyenne. Par ailleurs des calculs s'appuyant sur le programme de chimie quantique pcilo ont ete effectues pour une serie de composes analogues. Les resultats de ces deux approches (experimentale et theorique) sont discutes et critiques
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Larsson, Andreas. "Synthesis, structure and conformation of oligo- and polysaccharides." Doctoral thesis, Stockholm University, Department of Organic Chemistry, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-172.
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Carbohydrates are a complex group of biomolecules with a high structural diversity. Their almost omnipresent occurrence has generated a broad field of research in both biology and chemistry. This thesis focuses on three different aspects of carbohydrate chemistry, synthesis, structure elucidation and the conformational analysis of carbohydrates.
The first paper describes the synthesis of a penta- and a tetrasaccharide related to the highly branched capsular polysaccharide from Streptococcus pneumoniae type 37. In the second paper, the structure of the O-antigenic repeating unit from the lipopolysaccharide of E. coli 396/C1 was determined along with indications of the structure of the biological repeating unit. In addition, its structural and immunological relationship with E. coli O126 is discussed. In the third paper, partially protected galactopyranosides were examined to clarify the origin of an intriguing 4JHO,H coupling, where a W-mediated coupling pathway was found to operate. In the fourth paper, the conformation of methyl a-cellobioside is studied with a combination of molecular dynamics simulations and NMR spectroscopy. In addition to the expected syn-conformation, detection and quantification of anti-ø and anti-ψ conformers was also possible.
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Tabarin, Thibault. "Conformation et dynamique de biomolècules en phase gazeuse." Phd thesis, Université Claude Bernard - Lyon I, 2007. http://tel.archives-ouvertes.fr/tel-00198749.
Full textAbstract:
Nous avons développé une nouvelle expérience qui couple un spectromètre de masse de type piège ionique quadripolaire à un laser OPO UV-Visible accordable en longueur d'onde. Le travail qui est présenté dans cette thèse, est une étude des propriétés optiques et de la photofragmentation en phase gazeuse d'acides aminés, de peptides, d'ADN et de systèmes complexes métal-biomolécule. Dans le cas des peptides, l'excitation UV des chromophores contenus dans ces systèmes conduit à une fragmentation spécifique qui peut être contrôlée en fonction de la longueur d'onde. Les schémas de fragmentation obtenus après excitation laser dépendent des transferts de charge photo induits et peuvent être reliés à la géométrie du système.
Les spectres optiques des complexes d'agrégat d'argent tryptophane, supportés par des calculs de TD-DFT, ont permis une étude détaillée de l'excitation électronique, des transferts de charge et de la relaxation dans un système hybride métal biomolécule.
La production et l'utilisation de fragments radicalaires obtenus par photofragmentation ou par photodétachement sont également discutées et illustrées sur des peptides et de l'ADN.
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Sahoo, Daisy. "Probing the lipid-bound conformation of apolipophorin III." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ60341.pdf.
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Larsson, E. Andreas. "Synthesis, structure and conformation of oligo- and polysaccharides /." Stockholm : Institutionen för organisk kemi, Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-172.
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Davis, Tina Marie. "Optical properties, conformation, and thermodynamics of DNA oligonucleotides." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/30389.
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Wooten, E. Wrenn. "Structure, conformation and dynamics of N-linked oligosaccharides." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253421.
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Grant, Ian M. "Conformation and Catalysis in Lysozyme. A computational study." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520175.
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Aidibe, Ali. "Inspection des pièces flexibles sans gabarit de conformation." Mémoire, École de technologie supérieure, 2014. http://espace.etsmtl.ca/1301/7/AIDIBE_Ali.pdf.
Full textAbstract:
Le travail présenté dans le cadre de cette thèse porte sur l’automatisation de l’inspection dimensionnelle et géométrique d’une catégorie spécifique de pièces dites flexibles (ou souples). L’objectif principal est de manipuler ce type de composantes et leur nuage de points, qui représentent un scan pris à l’état libre, de manière virtuelle dans le but d’éliminer l’utilisation couteuse des gabarits de conformité et qui posent des problèmes de productivité pour les entreprises manufacturières. La thèse est organisée par articles. Le travail est reparti sur quatre phases. Les premières trois phases sont présentées par trois articles de revue et la quatrième phase est présentée dans une annexe.
La première phase de ce travail est une amélioration substantielle du module d’identification d’un outil d’inspection mathématique existant « IDI : The Iterative Displacement Inspection » et qui a été développé par l’équipe de recherche qui travaille sous la direction du professeur Tahan à l’ÉTS. Le module d’identification vise à distinguer les défauts qui sont dus au processus de fabrication des déformations qui sont dues à la flexibilité de la pièce (effets de gravité et effets des contraintes résiduelles). Nous proposons de remplacer le module original par un nouveau qui est basé sur les statistiques extrêmes. Nous démontrons que le nouveau module réduit considérablement les erreurs de type I et II. En plus, contrairement à la méthode d’identification de l’IDI, la méthode proposée n’exige aucun seuil spécifié par l’utilisateur.
Dans la deuxième phase de ce travail, nous proposons une approche originale pour quantifier la flexibilité/rigidité des composantes mécaniques. Nous introduisons un facteur qui représente le rapport entre le déplacement maximal résultant de la déformation de la pièce et sa tolérance de profil et nous présentons le tout sur une échelle logarithmique. Trois différentes zones ont été définies donnant une idée claire à l’industrie manufacturière de la situation des pièces sur l’échelle de la flexibilité. Par la suite, nous proposons une nouvelle méthode pour l’inspection des pièces flexibles sans gabarit de conformation : la méthode « IDB-CTB: Inspection of Deformable Bodies by Curvature and Thompson-Biweight ». Cette approche combine l’estimation de la courbure gaussienne, une des propriétés intrinsèques de la surface et qui est invariante sous les transformations isométriques, avec une méthode d’identification basée sur les statistiques extrêmes (Thompson-Biweight test). Le faible pourcentage d’erreur obtenue au niveau de l’estimation du défaut de profil ainsi que de l’aire de la zone de défaut reflète l’efficacité de l’approche.
Dans la troisième phase de cette thèse, nous proposons une autre approche, originale et complémentaire à celle de la deuxième phase. En plus de la détection des défauts de profil, nous visons à détecter les défauts de localisation. Nous introduisons deux critères qui correspondent aux spécificités des pièces mécaniques souples : la conservation de la distance curviligne et la minimisation entre deux objets (distance de Hausdorff). Nous adaptons et nous automatisons l’algorithme Coherent Point Drift, un puissant algorithme de recalage non rigide très employé dans l’imagerie médicale et d’animation, pour qu’il satisfasse ces deux critères. Nous obtenons de résultats satisfaisants en appliquant cette troisième approche sur une pièce flexible typique du secteur aérospatial.
La conclusion de cette thèse résume les contributions scientifiques générées par nos travaux sur l’inspection des pièces flexibles ainsi que les perspectives en relation avec ce sujet. En annexe, nous présentons une interface graphique (GUI) qui a été créée pour manipuler les
approches proposées ainsi que la banque des études de cas développée dans le cadre du stage industriel effectué chez Bombardier Aéronautique.
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Pritchford, Nigel Aaron. "Studies of conformation and configuration using crystallographic methods." Thesis, Durham University, 1994. http://etheses.dur.ac.uk/5365/.
Full textAbstract:
This Thesis demonstrates the use of the Cambridge Crystallographic Database for structure correlation studies in two very different fields. The first part of the Thesis (Chapters 2 and 3) is concerned with the systematic conformational analysis of medium-sized rings and satisfies the objectives of the study by: (i) applying novel classification techniques to the conformational descriptions of both the seven- and eight-membered rings, (ii) interpreting the results in terms of the relevant conformational hypersurface by locating the highly populated regions of that hypersurface and mapping the interconversion pathways, (iii) studying, modifying and improving the available methodologies for data analysis, and (iv) relating the conformational minima found using these methods to both the chemical environments of the fragments under investigation, and to energetic features of the hypersurface obtained by computational methods. The second major structure correlation experiment involves the analysis and description of 3-coordinated transition metal complexes using both simple geometrical models and group-theoretically based symmetry deformation coordinates. Non-bonded interactions will be seen to play a significant part in the geometry of the 3-coordinated fragment, and extrapolation of these results leads to the rationalisation of an addition/elimination scheme linking 4- and 2-coordinated fragments through the intermediate 3-coordinated species. Chapter 5 describes the crystallographic structure determinations of eight novel compounds: 3,5-cycloheptadienyl-3,5 dinitrobenzoate [C(_14)H(_12)O(_6)N(_2)]; a 34-membered diolide [C(_32)H(_60)O(_4)]; l-iodo-3-tosyloxy-propan-2-ane [C(_10)H(_11)O(_4)IS)]; 1β, 9 β -diacetyl- 7α-chloro-cis-hydrindane [C(_13)H(_19)O(_2)CI]; (R,R)-l,4-bis (2'-chloro-1 '-hydoxyethyl) benzene [C(_10)H(_12)O(_2)CI(_2)]; a fused penta-cyclic ring compound [C(_17)H(_14)]; 1,4 dibenzyl- 1,2,4,5-tetraazacyclohexane [C(_16) H(_20) N(_4)]; 1,5-di (2'-chloroacetoxy)-3,3-dimethyl-2,4- diphenyl-3-silapentane [C(_22)H(_26)O(_4) CI(_2) Si].
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Barker, John Joseph. "Structure and conformation in phosphines and metal complexes." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241511.
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Wang, Cheuk-san 1971. "Determining molecular conformation from distance or density data." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/16736.
Full textAbstract:
Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.Includes bibliographical references (p. 126-130).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
The determination of molecular structures is of growing importance in modern chemistry and biology. This thesis presents two practical, systematic algorithms for two structure determination problems. Both algorithms are branch-and-bound techniques adapted to their respective domains. The first problem is the determination of structures of multimers given rigid monomer structures and (potentially ambiguous) intermolecular distance measurements. In other words, we need to find the the transformations to produce the packing interfaces. A substantial difficulty results from ambiguities in assigning intermolecular distance measurements (from NMR, for example) to particular intermolecular interfaces in the structure. We present a rapid and efficient method to simultaneously solve the packing and the assignment problems. The algorithm, AmbiPack, uses a hierarchical division of the search space and the branch-and-bound algorithm to eliminate infeasible regions of the space and focus on the remaining space. The algorithm presented is guaranteed to find all solutions to a pre-determined resolution. The second problem is building a protein model from the initial three dimensional electron density distribution (density map) from X-ray crystallography. This problem is computationally challenging because proteins are extremely flexible.
(cont.) Our algorithm, ConfMatch, solves this "map interpretation" problem by matching a detailed conformation of the molecule to the density map (conformational matching). This "best match" structure is defined as one which maximizes the sum of the density at atom positions. The most important idea of ConfMatch is an efficient method for computing accurate bounds for branch-and-bound search. Confmatch relaxes the conformational matching problem, a problem which can only be solved in exponential time (NP-hard), into one which can be solved in polynomial time. The solution to the relaxed problem is a guaranteed upper bound for the conformational matching problem. In most empirical cases, these bounds are accurate enough to prune the search space dramatically, enabling ConfMatch to solve structures with more than 100 free dihedral angles.
by Cheuk-san (Edward) Wang.
Ph.D.
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Nativio, Raffaella. "Chromatin conformation at the IGF2-H19 imprinted locus." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609006.
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Bhardwaj, Shweta. "Interplay between chromatin conformation and transcription in eukaryotes." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:7395c490-a296-48e8-b8ca-afd785d516b0.
Full textAbstract:
The three-dimensional organization of the genome is important for various processes such as transcription, replication, and repair. Several studies have shown that the genome is organized into long-range and short-range chromatin loops. Gene loops represent a short-range chromatin loop, synonymous with the juxtaposition of promoter and terminator regions of a gene. In Chapter III, I investigate the mechanism of gene-loop formation in a constitutively expressed gene, mouse serum albumin (Alb). The Alb locus appears to exist in a clover-leaf structure, with the promoter in close physical proximity with an upstream enhancer and downstream genic sequences. Furthermore, Alb forms a promoter-terminator gene loop that is dependent on serine 2 phosphorylation of RNA polymerase C-terminal domain. I also investigate the presence of gene loop conformation at the human Nuclear factor NF-kappa-B (NFκB1) gene. In response to cytokine stimulation, NFκB1 transcription proceeds as a wave, with nascent RNA appearing as RNA polymerase traverses along the gene length. This coincides with formation of transient contacts between NFκB1 promoter and genic regions. The cohesin complex is a key mediator of chromatin loops and sister chromatid cohesion. The association of cohesin with chromatin is dependent on the loading complex, Mis4/Ssl3. In Chapter IV, I provide direct evidence for two functionally different populations of cohesin is Schizosaccharomyces pombe. Cohesin that co-localizes with Mis4 represents "cohesive" cohesin. In contrast, cohesin alone is unable to maintain stable sister chromatid cohesion, therefore, "less-cohesive" cohesin. Cohesive cohesin ensures stable cohesion because it is acetylated by the Eso1 acetyltransferase, which preferentially interacts with Mis4. In contrast, less-cohesive cohesin may function in recombination/repair. In Chapter V, I have identified a novel interplay between cohesin loading and transcription by RNA polymerase II. Inhibition of transcription initiation results in loss of Mis4 and consequently, cohesin binding on chromosomal arms regions. Furthermore, cohesin and Mis4 physically interact with RNA polymerase II. In Chapter VI, I summarize the above findings and propose a model that describes the stepwise loading of cohesin onto chromosomal arms during the fission yeast cell cycle. To conclude, I discuss the importance of understanding cohesin and its functions in health and diseases.
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Tabarin, Thibault. "Dynamique et conformation de biomolécules en phase gazeuse." Lyon 1, 2007. http://tel.archives-ouvertes.fr/docs/00/19/87/49/PDF/These_T.Tabarin_Dedie.pdf.
Full textAbstract:
Nous avons développé une nouvelle expérience qui couple un spectromètre de masse de type piège ionique quadripolaire à un laser OPO UV-Visible accordable en longueur d’onde. Le travail qui est présenté dans cette thèse, est une étude des propriétés optiques et de la photofragmentation en phase gazeuse d’acides aminés, de peptides, d’ADN et de systèmes complexes métal-biomolécule. Dans le cas des peptides, l’excitation UV des chromophores contenus dans ces systèmes conduit à une fragmentation spécifique qui peut être contrôlée en fonction de la longueur d’onde. Les schémas de fragmentation obtenus après excitation laser dépendent des transferts de charge photo induits et peuvent être reliés à la géométrie du système. Les spectres optiques des complexes d’agrégat d’argent tryptophane, supportés par des calculs de TD-DFT, ont permis une étude détaillée de l’excitation électronique, des transferts de charge et de la relaxation dans un système hybride métal biomolécule. La production et l’utilisation de fragments radicalaires obtenus par photofragmentation ou par photodétachement sont également discutées et illustrées sur des peptides et de l’ADNWe have developed a new experimental set-up which couple a quadrupole ion trap mass spectrometer with a tuneable UV-Visible laser OPO. This thesis’s work deals with the optical properties and the photofragmentation of amino acids, peptides, DNA and silver cluster tryptophan complexes in gas phase. In the case of peptides, the UV excitation of chromophores in the systems leads to a specific fragmentation which can be controlled by laser wavelength. The fragmentation schemes obtained after laser excitation depends on the photo-induced charge transfer and can be linked to the system’s geometry. The optical spectra of the silver cluster tryptophan complexes supported by TD-DFT calculations allow an elaborate study of the electronics excitation, charge transfer and relaxation in a hybrid metal biomolecule system. The production and use of the radical fragment produce by photofragmentation or by photodetachment are also discussed and exemple on peptides and DNAs are further illustrated
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Zhong, Shi. "Vers la synthèse de cyclonucléosides à conformation restreinte." Poitiers, 2007. http://www.theses.fr/2007POIT2325.
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Les molécules utilisées en thérapeutique contre le HIV (Virus d’Immunodéficience Humaine) responsable du SIDA et le HCV (Virus de l’Hépatite C) sont principalement des nucléosides modifiés telles la zidovudine et la ribavirine. En dépit du succès des analogues de nucléosides en chimie antivirale, ces composés provoquent des effets secondaires et conduisent souvent à des mutations ponctuelles de l’enzyme. Les nucléosides possédant des conformations particulières nécessaires à leur activité à chaque étape de leur métabolisation, différents analogues nucléosidiques à conformation restreinte associant la base hétérocyclique ont été préparés pour établir la conformation nécessaire pour une activité optimale. La synthèse de ces nouveaux nucléosides a mis en jeu des réactions variées comme la réaction de type Heck, la cyclisation de type métathèse et la métathèse croisée, l’addition 1,2 sur des aldéhydes ou époxydes, la N-glycosylation. Après optimisation ab initio de la géométrie en phase gaz selon la méthode de calcul de structure électronique B3LYP 6-31G(d,p) de Gaussian 03 et étude de la conformation en solution par RMN, les nouveaux composés ainsi préparés ont été testés pour leur activité antiviraleMolecules used in therapeutics against the HIV (Human Immunodeficiency Virus) responsible for the AIDS and the HCV (Virus of the Hepatitis C) are mainly modified such the zidovudin and the ribavirin. Despite the success of the nucleoside analogues in antiviral chemistry, these compounds gave side effects and often lead to punctual alterations of the enzyme. Nucleosides possessing particular conformations necessary for their activity in every stage of their metabolism pathway, various nucleoside analogues having restricted conformation associating the heterocyclic base were prepared to establish the necessary conformation for an optimal activity. The synthesis of these novel nucleosides involved various reactions such as Heck reaction, the Ring Closing Metathesis and the Cross Metathesis, the 1,2- addition on aldehydes or epoxides, the N-glycosylation. After ab initio gas-phase geometry optimization using B3LYP 6-31G(d,p) in the Gaussian 03 program package and conformational study in solution by NMR, the novel compounds were evaluated for their antiviral activity
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Boothroyd, Stephen. "Peptide self-assembly : controlling conformation and mechanical properties." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/peptide-selfassembly-controlling-conformation-and-mechanical-properties(ab641161-2b90-4b14-b081-259b063a0abf).html.
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In recent years a great deal of research has focussed on understanding and exploiting self assembling peptides as they form fibrillar hydrogels for use in a variety of different applications, such as tissue engineering and drug delivery. A particular class of such peptide systems are ionic-complementary peptides, composed of alternating hydrophobic and hydrophilic amino acids. Their simple structure is generally seen to assemble into β sheet rich fibrils, and easy modification of the primary structure is possible to allow the inclusion of recognition motifs tailored for a specific use. This can be done simply via physical mixing. To maximise the potential of such systems it is important to understand the interactions that govern the self-assembly behaviour. Here a variety of different peptides have been studied to elucidate control of peptide conformation and fibril morphology. The ability to easily tune the mechanical strength of the hydrogel has been explored by mixing peptide systems. The peptide FEFEFKFK (FEKII) was seen to assemble into β sheet rich fibrils of ~3 nm in diameter. Control of pH and hence the charge state of the E and K side chains altered sample properties. Gelation at pH 2.8 occurred at a concentration between 20 30 mg ml 1. At pH 4, 5 and 10 where the peptide has a lower net charge gelation was lowered to ~10 mg ml 1. Mechanical properties varied with G' values of 20-1200 Pa as pH was altered. Stronger gels were formed with lower net peptide charge. Hierarchical fibre assembly was observed for positively charged peptides, with fibres forming from lateral association of fibrils. Negatively charged peptides at pH 10 showed no such hierarchical assembly, and lower fibril persistence length. This was related to the change in charge along the fibril structure. At pH 7, where the peptide has no net charge, precipitation occurred. This showed a net charge was required on the peptide to disperse fibrils and prevent aggregation. The work showed the importance of ionic-interactions in determining both network morphology and bulk properties, and also elucidated control of such behaviour. AEAEAKAK (AEKII) was shown to assemble into α helix fibres. Alanine (A) is less hydrophobic than F, and is a known helix former. The role of F and A in assembly was assessed by the design of peptides FEAEFKAK (FAIEKII) and FEFEAKAK (FAIIEKII). Mixing A with F disrupted the peptides' ability to form a β sheet network by lowering the driving force for assembly given by the F residues. Trace amounts of β sheet were observed at low concentration, but at a critical concentration β sheet content increased and gelation occurred. This was found to be pH dependent. FAIEKII formed β-sheet fibrils at a lower concentration than FAIIEKII. While FAIEKII was able to assemble into different fibril structures, FAIIEKII showed no specific aggregation. This not only highlighted the importance of Hydrophobicity as a key driving force to assembly but also how the grouping of these amino acids in the primary sequence can determine the overall assembly characteristics of the peptide. The peptides FEFEFKFKGGFEFEFKFK (FEKII18-1) and FEFEFKFKGGFKFKFEFE (FEKII18-2) were designed to co-assemble with FEKII. Individually both peptides were seen to assemble into β sheet fibrils. FEKII18-1 formed fibrils of 2.3 3.1 nm in size, a result of folding along the chain caused by intra molecular attractive ionic interactions. FEKII18-2 formed larger fibrils of 4.4 5.2 nm from a straightened peptide chain given by the change in charge distribution. When co assembled with FEKII mechanical properties were enhanced, with G' increasing from 40 Pa at 20 mg ml 1 to 2400 Pa, depending on the concentration of FEKII18-1/FEKII18-2 added to the system. This was a result of these peptides providing fibril connections acting as cross links. This work has detailed control over the assembly process via peptide conformation and fibril interactions and the effect this has on overall macroscopic sample properties. This is vital in determining the viability of such systems in various biomedical applications.