Dissertations / Theses on the topic 'Protein flexibility'
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Mitchell, Felicity. "Modelling protein flexibility using molecular simulation methods." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525167.
Full textBroadhead, Richard Ian. "Metabolic flexibility in Escherichia coli." Thesis, University of Aberdeen, 1998. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU104201.
Full textMagnusson, Ulrika. "Structural Studies of Binding Proteins: Investigations of Flexibility, Specificity and Stability." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3640.
Full textZöllner, Frank G. "Enhancing protein-protein docking by new approaches to protein flexibility and scoring of docking hypotheses." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972854142.
Full textDobbins, Sara E. "Computational Studies of Protein Flexibility using Normal Mode Analysis." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508940.
Full textKoch, Kerstin. "Statistical analysis of amino acid side chain flexibility for 1:n protein protein docking." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968919413.
Full textSánchez, Martínez Melchor. "Protein Flexibility: From local to global motions. A computational study." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/288044.
Full textLa presente tesis se centra en el estudio computacional de la dinámica de las proteínas. Las proteínas son entidades flexibles y como tales se mueven. Este movimiento es indispensable y esta directamente relacionado con su función. La dinámica de las proteínas se puede dividir en dos grandes bloques conceptuales según el número de átomos involucrados, la escala de tiempo en que tiene lugar y la amplitud y dirección de la misma. Debido a la importancia de estos fenómenos, emerge la necesidad de tener un conocimiento profundo sobre los mismos. Debido a ello, en esta tesis doctoral se ha tratado de dar respuesta a varios fenómenos observados en relación directa con la dinámica de las proteínas. Concretamente, hemos realizado estudios a nivel local, de 'centro activo', relacionados con la catálisis enzimática y el daño proteico, así como a nivel global, con la determinación y el análisis de conjuntos conformacionales de proteínas. Estos estudios, se han desarrollado usando métodos propios de la química, la bioquímica y la biofísica computacionales, los cuales se han mostrado como herramientas muy útiles a la hora de estudiar la dinámica. De todos ellos, de forma general, podemos concluir que los métodos computacionales son una herramienta eficaz y util para caracterizar la dinámica de las proteínas. Sin embargo, los métodos computacionales actuales presentan limitaciones y para resolverlos la incorporación de datos experimentales as como su correcta interpretación es crucial. Pero aunque los metodos computacionales necesitan de los experimentales, esta necesidad también se da de manera opuesta. La convergencia de los métodos experimentales y computacionales es clave para poder profundizar en el conocimiento de la dinámica de las proteínas.
Salmaso, Veronica. "Exploring protein flexibility during docking to investigate ligand-target recognition." Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3421817.
Full textI modelli di riconoscimento ligando-proteina si sono evoluti nel corso degli anni: dal modello chiave-serratura a quello di fit-indotto e selezione conformazionale, il ruolo della flessibilità proteica è diventato via via più importante. Capire il meccanismo di riconoscimento è di grande importanza nella progettazione di nuovi farmaci, perchè può dare la possibilità di razionalizzare l’attività di ligandi noti e di ottimizzarli. L’applicazione di tecniche computazionali alla scoperta di nuovi farmaci risale agli anni ‘80, con l’avvento del cosiddetto “Computer-Aided Drug Design”, o, tradotto, progettazione di farmaci aiutata dal computer. Negli anni sono state sviluppate molte tecniche che hanno affrontato il problema della flessibilità proteica. Questo lavoro propone una strategia per considerare la variabilità delle strutture proteiche nel docking, attraverso un approccio combinato ligand-based/structure-based e attraverso lo sviluppo di una procedura completamente automatizzata di docking incrociato. In aggiunta, viene proposta una piena esplorazione della flessibilità proteica durante il processo di legame attraverso la Dinamica Molecolare Supervisionata. L’applicazione di un algoritmo simil-tabu alla dinamica molecolare classica accelera il processo di riconoscimento dalla scala dei micro-millisecondi a quella dei nanosecondi. Nel presente lavoro è stata fatta un’implementazione di questa algoritmica per studiare il processo di riconoscimento peptide-proteina.
Cobb, Andrew Martin. "Resolving the flexibility and intricacy of DNA repair protein-DNA interactions." Thesis, University of East Anglia, 2010. https://ueaeprints.uea.ac.uk/10586/.
Full textYu, Hongtao. "Water in Protein Cavities: Free Energy, Entropy, Enthalpy, and its Influences on Protein Structure and Flexibility." ScholarWorks@UNO, 2011. http://scholarworks.uno.edu/td/341.
Full textApgar, James R. (James Reasoner). "Modeling the flexibility of alpha helices in protein interfaces : structure based design and prediction of helix-mediated protein-protein interactions." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/43778.
Full textVita.
Includes bibliographical references.
Protein-protein interactions play an essential role in many biological functions. Prediction and design of these interactions using computational methods requires models that can be used to efficiently sample structural variation. This thesis identifies methods that can be used to sample an important sub-space of protein structure: alpha helices that participate in protein interfaces. Helices, the global structural properties of which can be described with only a few variables, are particularly well suited for efficient sampling. Two methods for sampling helical backbones are presented: Crick parameterization for coiled coils and normal-mode analysis for all helices. These are shown to capture most of the variation seen in the PDB. In addition, these methods are applied to problems in protein structure prediction and design. Normal-mode analysis is used to design novel nanomolar peptide inhibitors of the apoptosis-related Bcl-2 family member, Bcl-xL, and a modification of Crick Parameterization is used to predict the binding orientation of dimeric coiled coils with greater than 80% accuracy. Finally, this study addresses the increase in computational time required by flexible-backbone methods and the use of cluster expansion to quickly map structural energies to sequence-based functions for increased efficiency.
by James R. Apgar.
Ph.D.
Regmi, Chola K. "Structural Flexibility and Oxygen Diffusion Pathways in Monomeric Fluorescent Proteins." FIU Digital Commons, 2014. http://digitalcommons.fiu.edu/etd/1122.
Full textCrevenna, Escobar Alvaro Hernan. "Kinesin-1 mechanical flexibility and motor cooperation." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2007. http://nbn-resolving.de/urn:nbn:de:swb:14-1193308684832-88632.
Full textBuonfiglio, Rosa <1985>. "Computational strategies to include protein flexibility in Ligand Docking and Virtual Screening." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6330/1/Tesi_Buonfiglio.pdf.
Full textBuonfiglio, Rosa <1985>. "Computational strategies to include protein flexibility in Ligand Docking and Virtual Screening." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6330/.
Full textFischer, Nina M. [Verfasser], and Oliver [Akademischer Betreuer] Kohlbacher. "Modeling Flexibility of Protein-DNA and Protein-Ligand Complexes using Molecular Dynamics / Nina M. Fischer ; Betreuer: Oliver Kohlbacher." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1162896728/34.
Full textCrevenna, Escobar Alvaro Hernan. "Kinesin-1 mechanical flexibility and motor cooperation." Doctoral thesis, Technische Universität Dresden, 2006. https://tud.qucosa.de/id/qucosa%3A23868.
Full textSun, Li. "Advances in the use of phosphorescence spectroscopy as a probe of protein flexibility." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq30395.pdf.
Full textLong, Yun Chau. "Skeletal muscle metabolic flexibility: the roles of AMP-activated protein kinase and calcineurin /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-152-4/.
Full textJaya, Nomalie Naomi. "SUBSTRATE BINDING SITE FLEXIBILITY OF SMALL HEAT SHOCK PROTEINS AND FACTORS CONTRIBUTING TO EFFICIENT CHAPERONE ACTIVITY." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/193550.
Full textRadford, Sheena Elizabeth. "Domains and conformational flexibility in the catalytic mechanism of the 2-oxo acid dehydrogenase complexes." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236036.
Full textPallara, Chiara. "Structural Modeling and Characterization of Protein Interactions of Biomedical Interest: The Challenge of Molecular Flexibility." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/385987.
Full textLas proteínas son grandes biomoléculas que desarrollan funciones esenciales en las células, muy a menudo mediante la formación de complejos altamente específicos con otras proteínas y biomoléculas. Por tanto, uno de los mayores retos científicos en la actualidad es el estudio completo a nivel estructural y energético de todas las interacciones entre proteínas de interés biológico y terapéutico. Sin embargo, la consideración precisa de la plasticidad de las proteínas en los métodos computacionales de modelado molecular no es trivial, debido a limitaciones tanto técnicas como metodológicas. En este contexto, el objetivo principal de esta tesis doctoral ha sido el desarrollo, aplicación y evaluación de herramientas computacionales para la caracterización estructural, energética y dinámica de las proteínas y sus interacciones. Para cumplir con estos objetivos, durante la primera parte de la tesis se ha llevado a cabo la revisión de varios protocolos computacionales para la caracterización de las superficies de interación entre proteínas. Los métodos analizados proporcionan unas predicciones razonablemente consistentes y fiables. También se ha llevado a cabo la evaluación de la eficacia predictiva de nuestro método pyDock en CAPRI, un experimento comunitario de evaluación de métodos de modelado estructural de complejos entre proteínas. En general, a pesar de los avances metodológicos en los protocolos de docking, el modelado eficaz de la plasticidad de las proteínas sigue siendo un reto importante en el campo. En base a los análisis anteriores, se ha llevado a cabo un estudio sistemático sobre la importancia de la heterogeneidad conformacional en el reconocimiento entre proteínas. Los resultados indican que los ensamblados conformacionales generados a partir de proteínas en solución contienen confórmeros con mejor complementariedad energética que la estructura cristalográfica de dichas proteínas y que favorecen su reconocimiento intermolecular. A partir de estos resultados, se ha propuesto un nuevo métodode docking que usa ensamblados conformacionales generados a partir de las proteínas en solución. Esta estrategia resulta particularmente efectiva en casos poco o medianamente flexibles. Finalmente, en la última parte de la tesis se ha llevado a cabo la aplicación de métodos computacionales al modelado de varios casos de interés biomédico. En conclusión, los avances metodológicos en cuanto al modelado de proteínas y sus interacciones, junto a la inclusión eficaz de la flexibilidad conformacional, permiten tener herramientas computacionales cada vez más útiles para complementar los datos experimentales y mejorar la comprensión de procesos biológicos relevantes.
Kolar, Michal. "Statistical Physics and Message Passing Algorithms. Two Case Studies: MAX-K-SAT Problem and Protein Flexibility." Doctoral thesis, SISSA, 2006. http://hdl.handle.net/20.500.11767/4659.
Full textMunz, Marton. "Computational studies of protein dynamics and dynamic similarity." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:2fb76765-3e43-409b-aad3-b5202f4668b3.
Full textTripathi, Swarnendu. "Conformational Transition Mechanisms of Flexible Proteins." Kent State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1281491004.
Full textMittal, Seema. "Role of Protein Flexibility in Function, Resistance Pathways and Substrate Recognition Specificity in HIV-1 Protease: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/573.
Full textCeres, Nicoletta. "Coarse-grain modeling of proteins : mechanics, dynamics and function." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10030.
Full textProteins are flexible molecules, which accomplish a variety of cellular tasks through mechanical motions and conformational fluctuations encoded in their three-dimensional structure. Amongst the theoretical approaches contributing to a better understanding of the relationship between protein structure, mechanics, dynamics and function, coarse-grain models are a powerful tool. They can be used to integrate structural and dynamic information over broad time and size scales at a low computational cost, achieved by averaging out the less important degrees of freedom. In this work, fast comparative studies of protein flexibility and mechanics have been performed with the simple coarse-grain Elastic Network Model. However, the dependency of the results on the starting conformation, and the rather constrained backbone dynamics imposed by the harmonic approximation, motivated the development of a new approach, for a more extensive exploration of conformational space. These efforts led to the PaLaCe model, designed to allow significant changes in secondary structure, while maintaining residue specificity despite a lower-level resolution. Using PaLaCe, we were able to reproduce two processes involving protein plasticity: the mechanical unfolding of the I27 domain of the giant muscle protein titin and the near-native dynamics of two homologous enzymes adapted to work at different temperatures. Agreement with experimental data and results from published atomistic models demonstrate that PaLaCe is a reliable, sufficiently accurate, but computationally inexpensive approach. It therefore opens the doors for a systematic investigation of the link between protein dynamics/mechanics and function
Pondaven, Simon Pierre. "Conformational Flexibility and Amyloid Core Characterization of Human Immunoglobulin Light Chain Domains by Multidimensional NMR Spectroscopy." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1354113457.
Full textSCARAMOZZINO, DOMENICO. "Elastic Lattice Models: From Proteins to Diagrid Tall Buildings." Doctoral thesis, Politecnico di Torino, 2021. http://hdl.handle.net/11583/2872326.
Full textFRACCALVIERI, DOMENICO. "Comparison of protein dynamics: a new methodology based on self-organizing maps." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/19615.
Full textLorenzi, Magali. "Etude des transitions structurales dans les protéines flexibles par marquage de spin suivi par spectroscopie de Résonance Paramagnétique Electronique (RPE)." Thesis, Aix-Marseille 1, 2011. http://www.theses.fr/2011AIX10139/document.
Full textThe study of structural transitions in proteins is of crucial interest because these transformations are involved in many biological processes. Such structural phenomena can be the source of remarkable properties in flexible or disordered proteins, properties hardly accessible by conventional structural techniques. Site-directed spin labeling combined with electron paramagnetic resonance spectroscopy (EPR) is a technique well suited for the study of these structural transitions. The insertion of a nitroxide reagent on a cysteine, natural or introduced by site-directed mutagenesis, located in a key position of a protein provides local information on possible structural changes induced by the addition of a partner. This technique was applied on two biological systems with a different degree of flexibility. The flexibility of NarJ, a chaperon protein involved in the biogenesis of the complex nitrate reductase of Escherichia coli was studied in the presence of its peptide partner. These studies enabled us to determine the interaction site and to show that the association of the two partners induced a locked conformation of NarJ. The second system is the CP12 protein of Chlamydomonas reinhardtii, involved in the regulation of a supramolecular complex of the Calvin cycle. CP12 shares some similarities with the intrinsically disordered protein but having natural and functional cysteines. The conventional labeling allowed us to highlight a new role of its partner and to demonstrate that CP12 remains disordered in the complex. Moreover, this protein was used as a model system to develop a new labeling strategy on tyrosine and to demonstrate its feasibility
Leis, Simon [Verfasser], Martin [Akademischer Betreuer] Zacharias, and Iris [Akademischer Betreuer] Antes. "Impact of Protein conformational Changes on Molecular Docking - Design of a Docking Approach including Receptor Flexibility / Simon Leis. Gutachter: Iris Antes. Betreuer: Martin Zacharias." München : Universitätsbibliothek der TU München, 2012. http://d-nb.info/1030099464/34.
Full textD'Cunha, Cassian. "A molecular simulation study of the utility of methyl groups as probes of protein packing and flexibility and maintaining the computational environment for computational biomolecular research." FIU Digital Commons, 2003. http://digitalcommons.fiu.edu/etd/3020.
Full textSantiago, Daniel Navarrete. "Use and Development of Computational Tools in Drug Discovery: From Small Molecules to Cyclic Peptides." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4398.
Full textPASI, MARCO. "A dynamical perspective on cold-adapted enzymes at the molecolar level." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2009. http://hdl.handle.net/10281/7729.
Full textNguyen, Thi Minh-Ha. "Molecular recognition of ubiquitin and Lysine 63 linked diubiquitin by STAM2 : the effect of the linkers length and flexibility." Thesis, Lyon, 2019. https://n2t.net/ark:/47881/m6668chz.
Full textProtein-protein interaction is considered as an important field of research, as it is the key to control variable cell processes and pathways. In eucaryotic cells, multidomain proteins (MDPs), which consist of more than one domain, take up over 70 % of the pool. Those identical or different domains of a MDP are connected to each other by a linker of variable length and flexibility. For long flexible linker, it allows the protein to sample a wide range of conformation and to adjust interaction in a subtle way. Despite numerous efforts of research on the field, some issues remain unanswered or require further investigation. As part of this thesis, my work aims to define the role taken by the intrinsically disordered linker within MDPs. For that purpose, the STAM2 (Signal transducing adapter molecule 2) protein of the ESCRT (Endosomal Sorting Complexes Required for Transport) machinery was chosen to examine the effect of the flexibility and dynamics of the linker regions on the molecular recognition with ubiquitin and Lysine63-linked di-ubiquitin (K63-Ub2). Such efforts were carried out by designing specific mutants altering the linker regions in different ways. The various truncated versions undergo half or complete deletion of a domain or have their linker either shortened, deleted or modified in the amino acid composition. With a combination of the several biophysical methods namely NMR (Nuclear Magnetic Resonance) spin relaxation, SAXS (Small Angle X-ray Scattering) and CD (Circular Dichroism), the study has demonstrated that the alteration in the linker region modifies the flexibility and the dynamics of the protein, one among them possibly introduces slight change in conformation. Furthermore, the modification of the linker has an impact on the inter-domain motion and alter binding affinities between STAM2 constructs and di-ubiquitin without affecting domains integrity or binding sites. In brief, disordered linkers provide plasticity to the protein, which allow adaptability and specificity to molecular recognition process. As a further application, the linkers included in multidomain proteins could also be the next generation of druggable target as their modification may reduce or completely abolish interactions
Alonso, Hernan, and hernan alonso@anu edu au. "Computer Modelling and Simulations of Enzymes and their Mechanisms." The Australian National University. The John Curtin School of Medical Research, 2006. http://thesis.anu.edu.au./public/adt-ANU20061212.161155.
Full textAlves, Ariane Ferreira Nunes. "Um método computacional para estimar afinidades entre proteínas flexíveis e pequenos ligantes." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-08052013-144801/.
Full textComputational methods are used to generate protein-ligand complex structures and estimate their binding affinities. This work investigated how different representations of protein flexibility affect poses obtained by molecular docking and the affinities attributed to these poses. T4 lysozyme mutants L99A and L99A/M102Q were chosen as model systems. A descriptor for prediction of affinities based on linear interaction energy (LIE) approximation was parametrized specifically to lysozyme ligands and was used to estimate affinities. The protein was represented as a group of crystal structures or as structures from a molecular dynamics trajectory. OPLS-AA force field was used to model protein and ligands and the Generalized Born approximation was used to model solvent. The parametrized affinity descriptor resulted in average deviations between experimental and calculated affinities of 1.8 kcal/mol for a test set. Descriptor performance was satisfactory in the separation between crystal poses and false-positive ones and in the identification of false-positive poses. Clustering of complexes was tried out to reduce computational cost to estimate affinities, but results were poor. The best approximations to the implicit ligand theory proposed here in order to estimate affinities consider groups of receptor structures with the same weight. Ligand configurations also have the same weight or are dominated by only one configuration. The representation of protein flexibility requires an adequate statistical treatment when used to estimate affinities. Here, the linking between LIE and the implicit ligand theory proved itself useful.
Neto, Antonio Marinho da Silva. "Geometria diferencial e teoria da informação aplicada a análise de ensembles conformacionais de proteínas." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-07032018-150722/.
Full textOne of the major challenges of modern structural biology is how to deal with protein flexibility. Besides the experimental difficulties, a relatively overlooked theoretical challenge is the lack of a proper mathematical language to represent proteín conformational space. The most popular representations have severe limitations, which reflects on the difficulties associated with conformational ensemble analyses. However, differential geometry (GD) and information theory (TI) can help to overcome such difficulties and were not well explored in this context. Here we investigate the usage of DG and TI as a mathematical representation of protein conformational space applied to the analyses of conformational ensembles. The DG descriptors calculation consists of representing protein backbone as a spatial curve and describes it by its curvature, κ, and torsion, τ . Based on those values, the distance between conformation and flexibility measurements were defined and a clustering algorithm was applied to identify conformational states. For the application of TI, a coding system for DG descriptors was developed to express each conformation as a sequence of finite symbols. Based on those sequences, information measurements associated to a residue, Rres, and to a conformation, Rconf , were defined. To investigate its efficacy, the proposed method was applied to conformation ensembles of three test systems: 1) Ubiquitin, 2) E1-DBD of HPV18 and 3) the steps of c-Myb-KIX binding. The DG analyses show equally good or superior performance when compared with popular methods on all tested system. In addition, the methods are especially useful to monitoring helix stability and analyses of very flexible proteins (or regions), since avoids the necessity of superposing structures. The values of Rconf are useful to compare different steps of a folding process and residues near regions involved in binding events tend to present higher values of Rres. However, those residues importance is uncertain and further studies are necessary to determinate if and how those can contribute to protein function. Nevertheless, the information measurements were informative on the comparison of compare conformational states and allow to formulate a testable hypothesis. On the other hand, the GD representation is computationally convenient, intuitive and avoid most of the limitations of the popular method applied to conformational ensemble analyses.
Gruza, Jan. "Modélisation de la flexibilité des glycannes complexes en solution et en interaction avec des protéines." Grenoble 1, 1998. http://www.theses.fr/1998GRE10158.
Full textIllingworth, C. J. R. "Structural and electrostatic flexibility in proteins:-computational approaches to ligand binding." Thesis, University of Essex, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486625.
Full textSekhi, Ikram. "Développement d'un alphabet structural intégrant la flexibilité des structures protéiques." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC084/document.
Full textThe purpose of this PhD is to provide a Structural Alphabet (SA) for more accurate characterization of protein three-dimensional (3D) structures as well as integrating the increasing protein 3D structure information currently available in the Protein Data Bank (PDB). The SA also takes into consideration the logic behind the structural fragments sequence by using the hidden Markov Model (HMM). In this PhD, we describe a new structural alphabet, improving the existing HMM-SA27 structural alphabet, called SAFlex (Structural Alphabet Flexibility), in order to take into account the uncertainty of data (missing data in PDB files) and the redundancy of protein structures. The new SAFlex structural alphabet obtained therefore offers a new, rigorous and robust encoding model. This encoding takes into account the encoding uncertainty by providing three encoding options: the maximum a posteriori (MAP), the marginal posterior distribution (POST), and the effective number of letters at each given position (NEFF). SAFlex also provides and builds a consensus encoding from different replicates (multiple chains, monomers and several homomers) of a single protein. It thus allows the detection of structural variability between different chains. The methodological advances and the achievement of the SAFlex alphabet are the main contributions of this PhD. We also present the new PDB parser(SAFlex-PDB) and we demonstrate that our parser is therefore interesting both qualitative (detection of various errors) and quantitative terms (program optimization and parallelization) by comparing it with two other parsers well-known in the area of Bioinformatics (Biopython and BioJava). The SAFlex structural alphabet is being made available to the scientific community by providing a website. The SAFlex web server represents the concrete contribution of this PhD while the SAFlex-PDB parser represents an important contribution to the proper function of the proposed website. Here, we describe the functions and the interfaces of the SAFlex web server. The SAFlex can be used in various fashions for a protein tertiary structure of a given PDB format file; it can be used for encoding the 3D structure, identifying and predicting missing data. Hence, it is the only alphabet able to encode and predict the missing data in a 3D protein structure to date. Finally, these improvements; are promising to explore increasing protein redundancy data and obtain useful quantification of their flexibility
Mejia, Tamayo Verónica. "Propriétés volumétriques des Arabinogalactan-protéines d'exsudats de gommes d'Acacia." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTG060/document.
Full textAcacia gum is the oldest and most widely known and used gum, it is a dried gummy exudate from the leaves and branches of the Acacia senegal and Acacia seyal trees. Acacia gums are weakly charged, amphiphilic hyperbranched arabinogalactan-proteins (AGPs). They are composed of about 90% polysaccharides and from 1-3% of proteins and minerals. In spite of the widely spread of industrial usage of A. gums, their volumetric properties (hydrostatic and hydrodynamic) have not been well studied. These properties have been linked to important properties such as flexibility and hydration of the molecule, which are related to important functional properties of A. gums (e. g. interfacial properties). The main objective of this PhD thesis was to study the volumetric properties of AGPs from Acacia gums exudates. For this effect, the main commercial species, A. senegal and A. seyal, and the macromolecular fractions of the former, obtained via hydrophobic interaction and ionic exchange chromatographies were studied. The main results showed that AGPs from Acacia gums have a semi-flexible structure. However, differences in their flexibility and hydration were seen among AGP fractions. These differences were explained based on their composition, polarity, molar mass, shape and conformation. Furthermore, an intermediate behavior between proteins and linear polysaccharides was evidenced. In addition, an effect of the presence of AGP based aggregates on the volumetric properties was seen
Ruzmetov, Talant A. "THE ROLE OF CHAIN FLEXIBILITY AND CONFORMATIONALDYNAMICS ON INTRINSICALLY DISORDERED PROTEINASSOCIATION." Kent State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1564588247414425.
Full textKahler, Anna [Verfasser], Heinrich [Akademischer Betreuer] Sticht, Timothy [Gutachter] Clark, and Heinrich [Gutachter] Sticht. "Intrinsic Flexibility and Structural Stability of Proteins / Anna Kahler ; Gutachter: Timothy Clark, Heinrich Sticht ; Betreuer: Heinrich Sticht." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2018. http://d-nb.info/1173422668/34.
Full textSchütz, Denise [Verfasser], Thomas F. [Gutachter] Prisner, and Volker [Gutachter] Dötsch. "Conformational flexibility of multi-domain proteins determined by pulsed EPR spectroscopy / Denise Schütz ; Gutachter: Thomas F. Prisner, Volker Dötsch." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2017. http://d-nb.info/1148548262/34.
Full textMenzel, Anja [Verfasser], Milton T. [Akademischer Betreuer] Stubbs, Ulrich [Akademischer Betreuer] Baumann, and Renate [Akademischer Betreuer] Ulbrich-Hofmann. "Flexibilität und Spezifität in Protein-Protein-Wechselwirkungen am Beispiel der Komplexbildung von Trypsin-Varianten und dem Proteaseinhibitor Eglin C / Anja Menzel. Betreuer: Milton T. Stubbs ; Ulrich Baumann ; Renate Ulbrich-Hofmann." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2009. http://d-nb.info/1024937135/34.
Full textBauman, Mariia A. "Characterizing the Effect of Conformational Changes in the Protein SufU on its Ability to Enhance Enzymatic Activity of the Cysteine Desulfurase SufS in Streptococcus mutans." Bowling Green State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1467906490.
Full textKapoor, Shobhna [Verfasser], Roland [Akademischer Betreuer] Winter, and Martin [Akademischer Betreuer] Engelhard. "Biophysical insights into the Ras-membrane ballet: orientational flexibility, conformational substates and mechanosensitivity of Ras proteins / Shobhna Kapoor. Betreuer: Roland Winter. Gutachter: Martin Engelhard." Dortmund : Universitätsbibliothek Dortmund, 2013. http://d-nb.info/1099297656/34.
Full textSilva, Júlio César da. "Estudos de macromoléculas biológicas parcialmente desestruturadas usando espalhamento de raios-X." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/277988.
Full textTese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin
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Resumo: As técnicas de caracterização estrutural de macromoléculas tradicionais se baseiam no fato de uma macromolécula possuir uma conformação compacta e estruturada. Partes flexíveis ou regiões desordenadas têm sido sempre consideradas como grandes obstáculos para técnicas como a cristalografia de raios-X e a ressonância magnética nuclear (RMN). A necessidade de entender a atividade funcional de proteínas nativamente desenoveladas e de proteínas flexíveis com múltiplos domínios tem adquirido grande importância recentemente, mesmo porque essas proteínas desafiam o paradigma de que uma proteína precisa de uma estrutura bem definida para ser funcional. É bem nesse ponto que a técnica de espalhamento de raios-X a baixos ângulos (SAXS) surge oferecendo ferramentas únicas para realizar estudos de macromoléculas flexíveis ou parcialmente desestruturadas, com aplicações muito bem sucedidas em polímeros, matéria mole e macromoléculas em solução. Neste trabalho de tese decidimos enfrentar o desafio de caracterizar proteínas que não possuem uma estrutura bem definida. A teoria do espalhamento mereceu especial cuidado para se adequar tanto aos métodos experimentais da técnica quanto aos tratamentos matemáticos em cálculos usados para estudar esse tipo de proteínas. Apresentamos aqui o estudo de duas proteínas pertencentes à classe das proteínas nativamente desenoveladas: (1) a proteína FEZ1, que é necessária para o crescimento de axônios; (2) a proteína Ki-1/57, que é encontrada em diversas células com câncer principalmente em tumores do sistema linfático. Estudamos também algumas proteínas com múltiplos domínios conectados por regiões flexíveis e que são: (1) duas chaperonas da classe das HSP40 (proteínas Sis1 e Ydj1) juntamente com construções onde alguns domínios dessas proteínas foram cortados; (2) a proteína ribonucléica heterogênea hnRNP-Q que está envolvida em importantes funções do RNA. Experiências de SAXS foram realizadas, fornecendo parâmetros dimensionais e informações de forma dessas proteínas em solução. Modelos de baixa resolução das possíveis conformações foram calculados a partir das curvas de SAXS usando métodos de modelagem ab initio combinados com modelagem de corpos rígidos. Os resultados forneceram informações importantes para elucidar as funções biológicas dessas proteínas. É importante ressaltar que, para realizar os estudos com proteínas em solução, é necessário contar com uma instrumentação adequada e devidamente montada para a aplicação da técnica de SAXS. Para isso, durante o período de desenvolvimento deste doutorado houve um grande investimento na montagem, teste e caracterização de instrumentos, junto à equipe de profissionais do Laboratório Nacional de Luz Síncrotron (LNLS), completando o comissionamento da estação experimental SAXS2 do LNLS
Abstract: The traditional techniques for structural characterization of macromolecules are based on a compact and structured conformation of the macromolecule. Flexible or disordered regions have usually been regarded as a great hindrance to techniques like X-ray protein crystallography and nuclear magnetic resonance (NMR). The need to study functional activity of natively unfolded proteins and flexible multidomain proteins came to the light rather recently, defying the classical structure¿function paradigm where a protein must have a well-defined 3-D structure to be functional. In this type of situation, the small-angle X-ray scattering (SAXS) technique appears as a unique tool to deal with this problem. Indeed, the application of SAXS methods to the characterization of soft matter (e.g. polymers) and macromolecules in solution has already succeeded during the last years. In this work we decided to face the challenge of characterizing proteins that do not have a well defined structure. The SAXS experimental technique as well as the mathematical methods and calculations needed special attention in order to be correctly applied to study the specific problem of unstructured proteins in solution. Thus, it was possible to find evidence of the structural details of these proteins and obtain a low resolution 3-D average structure. Here we present the study of two proteins that belong to the group of natively unfolded proteins: (1) The FEZ1 protein, which is necessary for axon growth, and (2) the proteins indentified as Ki-1/57, which is found in diverse cancer cells mainly in lymphatic systems tumors. We also studied some flexible multidomain proteins: (1) two chaperones from the groups of HSP40 (the proteínas Sis1 e Ydj1), and two mutant constructions where some domains were deleted; (2) the heterogeneous ribonucleoprotein hnRNP-Q which is related to an array of important functions of RNA. Several SAXS experiments were performed providing overall parameters and important shape information about those proteins in solution. Low resolution models for the possible conformations of these proteins were restored from the SAXS curves using ab initio modeling methods combined with rigid body modeling. The SAXS results provided a unique structural background for the biologists to deal with the function of these proteins. SAXS experiments with proteins in solution demand the use of a specific instrumentation properly developed for those studies. So, it is important to mention that, throughout the duration of this doctorate, specific instrumentation development and testing was done together with the technical staff of the Brazilian Synchrotron Light Laboratory (LNLS, Campinas, SP, Brazil), collaborating with the commissioning of the new SAXS2 workstation, completed in 2008
Doutorado
Física
Doutor em Ciências