Browsing by Author "Melo Ledermann, Francisco Javier"

Now showing 1 - 20 of 49
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    A Composite Score for Predicting Errors in Protein Structure Models
    (2006) Eramian, D.; Melo Ledermann, Francisco Javier
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    A Tool to Assist the Study of Specific Features At Protein Binding Sites
    (2003) Santander V; Melo Ledermann, Francisco Javier
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    Accurate and Unambiguous Tag-To-Gene Mapping in Serial Analysis of Gene Expression
    (2006) Malig, R.; Agosin T., Eduardo; Melo Ledermann, Francisco Javier
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    Adaptive Evolution of the Insulin Gene in Caviomorph Rodents
    (2005) Opazo, J.; Palma Vásquez, Ramón Eduardo; Melo Ledermann, Francisco Javier
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    All-atom knowledge-based potential for RNA structure prediction and assessment
    (2011) Capriotti, E.; Norambuena Arenas, Tomás.; Melo Ledermann, Francisco Javier
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    Análisis in vitro de los diferentes modos de unión a ADN de los factores de transcripción MarA y Rob
    (2021) Geoffroy Jarpa, Consuelo Ignacia; Melo Ledermann, Francisco Javier; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    El proceso de reconocimiento molecular entre proteínas y ADN es fundamental para la vida. MarA y Rob son 2 factores de transcripción de Escherichia coli pertenecientes a la familia AraC/XylS, cuyos miembros presentan una alta similitud de secuencia y se encuentran relacionados a la regulación de genes involucrados en resistencia a antibióticos, tolerancia estrés oxidativo y resistencia a disolventes orgánicos y metales pesados [1]. La estructura de ambas proteínas incluye un dominio de reconocimiento a ADN organizado en un motivo HTH bipartito, con dos hélices clave en el reconocimiento de secuencias (Hélices 3 y 6). Adicionalmente Rob presenta un dominio regulatorio en el extremo C-terminal, cuya función aún no es bien conocida. Estudios cristalográficos previos, sugieren que ambos factores de transcripción reconocen y se unen a sus secuencias promotoras de forma distinta. Mientras que MarA interactúa con dos secuencias nucleotídicas clave denominadas cajas A y B de la región promotora y une ambas hélices al surco mayor del ADN deformándolo, Rob reconoce ambas cajas, pero tan solo se une a una de ellas sin alterar la estructura nucleica. En este estudio se abordan diferentes interrogantes y se combinan e integran datos experimentales, estadísticos y computacionales lo que permite comprender los mecanismos de reconocimiento y las diferencias planteadas. El factor de transcripción purificado se agregó in vitro a los distintos promotores degenerados y las secuencias unidas y no unidas se separaron. La estrategia general fue crear una biblioteca de sitios de unión potenciales, a partir de las secuencias unidas. Ambos extremos de las secuencias de la biblioteca tienen sitios de unión de partidores de modo que pudieron amplificarse mediante PCR y ser secuenciados mediante secuenciación masiva. Por otro lado los promotores degenerados abarcaron tanto el promotor mar como el promotor micF completo y se fueron cubriendo regiones de 4 nucleótidos. Esto permitió tener una mirada global de los factores que juegan un rol importante en el reconocimiento específico proteína-ADN. Los resultados claves de este estudio son: en primer lugar que la presencia o ausencia del dominio regulatorio, jugaría un rol en la especificidad del reconocimiento proteína-ADN. En segundo lugar, la región espaciadora no aportaría especificidad a la unión, pero sí jugaría un papel clave en cuanto a la estabilidad de la unión. Y finalmente se concluye que Rob presenta dos modos de unión alternativos en donde presenta contacto directo con el surco mayor del ADN a través de la hélice 3 y la hélice 6 o bien interactúa principalmente sólo con caja A a través de hélice 3.
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    Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3 beta : autoregulation of GSK-3 beta in vivo
    (2015) Tapia Rojas, Cheril Cecilia; Schüller, Andreas; Lindsay, Carolina B.; Ureta, Roxana C.; Melo Ledermann, Francisco Javier; Mejías Reyes, Cristóbal; Hancke, Juan; Inestrosa Cantín, Nibaldo
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    Autosomal STR allele frequencies for the CODIS system from a large random population sample in Chile
    (2012) Vergara Saavedra, Ismael Antonio; Melo Ledermann, Francisco Javier
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    Calculation of accurate interatomic contact surface areas for the quantitative analysis of non-bonded molecular interactions
    (2019) Ribeiro, J.; Rios-Vera, C.; Melo Ledermann, Francisco Javier; Schüller, Andreas
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    Characterization of small RNAs in Xenopus tropicalis gastrulae
    (2012) Faunes Quinteros, Fernando Emerson; Melo Ledermann, Francisco Javier; Larraín Correa, Juan Agustín
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    Comparison of Different Melting Temperature Calculation Methods for Short Dna Sequences
    (2005) Panjkovich a; Melo Ledermann, Francisco Javier
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    Decorin Is Specifically Solubilized by Heparin From the Extracellular Matrix of Rat Skeletal Muscles
    (1993) Brandan, Enrique; Melo Ledermann, Francisco Javier
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    Derivando relaciones evolutivas entre las proteínas de cubierta de membrana mediante comparaciones estructurales
    (2021) Gutiérrez Espinosa, Fernando Ignacio; Melo Ledermann, Francisco Javier; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Las proteínas de cubierta de membranas (MC) cumplen un rol esencial en el transporte intracelular, permitiendo el intercambio de materiales entre los compartimientos especializados dentro de las células eucariotas. Las proteínas MC poseen una combinación única de dominios β-propeller/α-solenoide que les otorga la capacidad de deformar membranas. Su arquitectura y las señales de secuencia señalan que estas proteínas probablemente evolucionaron a partir de un ancestro común, pero la gran divergencia estructural lleva a sugerir que estas proteínas han cambiado considerablemente durante la evolución. Esto constituye un reto sobre todo para determinar relaciones evolutivas usando las herramientas disponibles basadas en comparación de secuencias y estructuras producto de la extrema divergencia observada entre estas proteínas. Actualmente no existe un claro consenso acerca de los diferentes tipos de arquitectura que existen entre las proteínas de cubierta de membranas y, en el estado del arte, solamente se han generado árboles filogenéticos cualitativos según las relaciones parciales encontradas entre sus miembros sin considerar comparaciones estructurales a gran escala de manera exhaustiva. Por ello, en el desarrollo de esta tesis se creó una nueva herramienta computacional para la comparación flexible de estructura de proteínas llamada MOMA2, que permite evaluar las similitudes estructurales entre proteínas muy divergentes mediante matrices de elementos de estructuras secundarias que nos permiten capturar la topología de las proteínas. Este programa ha sido diseñado para capturar las similitudes estructurales entre proteínas distantes mediante comparaciones estructurales flexibles, permitiéndonos clasificarlas según sus dominios y visualizar también el desplazamiento de cuerpo rígido de los sub-fragmentos encontrados equivalentes. Por ende, hemos utilizado esta herramienta para generar un nuevo esquema de clasificación de las proteínas de cubierta de membrana basado en la similitud estructural de sus dominios, permitiéndonos a la vez, construir árboles filogenéticos basados en comparaciones estructurales que confirman las relaciones conocidas, además permiten extender aquellas relaciones ya existentes y finalmente descubrir nuevas relaciones entre sus miembros. Por último, esta herramienta ha permitido reformular un modelo parsimonioso considerando las posibles combinaciones de dominios que pudieron dar origen a los diferentes arreglos de dominios que están presentes en las proteínas MC. En síntesis, el desarrollo de esta nueva herramienta nos ha permitido específicamente plantear los posibles pasos que dieron origen a las proteínas de cubierta de membrana a partir de las comparaciones de estructurales a pesar de la extrema divergencia que poseen estas proteínas. Por otro lado, desde una visión más general, esta herramienta nos abre nuevas posibilidades para explorar relaciones que aún permanecen ocultas debido a la extrema divergencia que poseen sus secuencias, pero que aún conservan sus similitudes estructurales.
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    Dnamate: a Consensus Melting Temperature Prediction Server for Short Dna Sequences
    (2005) Panjkovich a; Melo Ledermann, Francisco Javier
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    Effective knowledge-based potentials
    (2009) Ferrada, Evandro.; Melo Ledermann, Francisco Javier
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    Effects of Tetrahydrohyperforin in Mouse Hippocampal Slices : Neuroprotection, Long-term Potentiation and TRPC Channels
    (2014) Montecinos, C.; Schüller, Andreas; Parodi, J.; Melo Ledermann, Francisco Javier; Inestrosa Cantín, Nibaldo
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    Efficient and automated large-scale detection of structural relationships in proteins with a flexible aligner
    (2016) Gutiérrez, Fernando I.; Rodríguez Valenzuela, Felipe.; Ibarra, Ignacio L.; Melo Ledermann, Francisco Javier; Devos, Damien P.
    Abstract Background The total number of known three-dimensional protein structures is rapidly increasing. Consequently, the need for fast structural search against complete databases without a significant loss of accuracy is increasingly demanding. Recently, TopSearch, an ultra-fast method for finding rigid structural relationships between a query structure and the complete Protein Data Bank (PDB), at the multi-chain level, has been released. However, comparable accurate flexible structural aligners to perform efficient whole database searches of multi-domain proteins are not yet available. The availability of such a tool is critical for a sustainable boosting of biological discovery. Results Here we report on the development of a new method for the fast and flexible comparison of protein structure chains. The method relies on the calculation of 2D matrices containing a description of the three-dimensional arrangement of secondary structure elements (angles and distances). The comparison involves the matching of an ensemble of substructures through a nested-two-steps dynamic programming algorithm. The unique features of this new approach are the integration and trade-off balancing of the following: 1) speed, 2) accuracy and 3) global and semiglobal flexible structure alignment by integration of local substructure matching. The comparison, and matching with competitive accuracy, of one medium sized (250-aa) query structure against the complete PDB database (216,322 protein chains) takes about 8 min using an average desktop computer. The method is at least 2–3 orders of magnitude faster than other tested tools with similar accuracy. We validate the performance of the method for fold and superfamily assignment in a large benchmark set of protein structures. We finally provide a series of examples to illustrate the usefulness of this method and its application in biological discovery. Conclusions The method is able to detect partial structure matching, rigid body shifts, conformational changes and tolerates substantial structural variation arising from insertions, deletions and sequence divergence, as well as structural convergence of unrelated proteins.Abstract Background The total number of known three-dimensional protein structures is rapidly increasing. Consequently, the need for fast structural search against complete databases without a significant loss of accuracy is increasingly demanding. Recently, TopSearch, an ultra-fast method for finding rigid structural relationships between a query structure and the complete Protein Data Bank (PDB), at the multi-chain level, has been released. However, comparable accurate flexible structural aligners to perform efficient whole database searches of multi-domain proteins are not yet available. The availability of such a tool is critical for a sustainable boosting of biological discovery. Results Here we report on the development of a new method for the fast and flexible comparison of protein structure chains. The method relies on the calculation of 2D matrices containing a description of the three-dimensional arrangement of secondary structure elements (angles and distances). The comparison involves the matching of an ensemble of substructures through a nested-two-steps dynamic programming algorithm. The unique features of this new approach are the integration and trade-off balancing of the following: 1) speed, 2) accuracy and 3) global and semiglobal flexible structure alignment by integration of local substructure matching. The comparison, and matching with competitive accuracy, of one medium sized (250-aa) query structure against the complete PDB database (216,322 protein chains) takes about 8 min using an average desktop computer. The method is at least 2–3 orders of magnitude faster than other tested tools with similar accuracy. We validate the performance of the method for fold and superfamily assignment in a large benchmark set of protein structures. We finally provide a series of examples to illustrate the usefulness of this method and its application in biological discovery. Conclusions The method is able to detect partial structure matching, rigid body shifts, conformational changes and tolerates substantial structural variation arising from insertions, deletions and sequence divergence, as well as structural convergence of unrelated proteins.Abstract Background The total number of known three-dimensional protein structures is rapidly increasing. Consequently, the need for fast structural search against complete databases without a significant loss of accuracy is increasingly demanding. Recently, TopSearch, an ultra-fast method for finding rigid structural relationships between a query structure and the complete Protein Data Bank (PDB), at the multi-chain level, has been released. However, comparable accurate flexible structural aligners to perform efficient whole database searches of multi-domain proteins are not yet available. The availability of such a tool is critical for a sustainable boosting of biological discovery. Results Here we report on the development of a new method for the fast and flexible comparison of protein structure chains. The method relies on the calculation of 2D matrices containing a description of the three-dimensional arrangement of secondary structure elements (angles and distances). The comparison involves the matching of an ensemble of substructures through a nested-two-steps dynamic programming algorithm. The unique features of this new approach are the integration and trade-off balancing of the following: 1) speed, 2) accuracy and 3) global and semiglobal flexible structure alignment by integration of local substructure matching. The comparison, and matching with competitive accuracy, of one medium sized (250-aa) query structure against the complete PDB database (216,322 protein chains) takes about 8 min using an average desktop computer. The method is at least 2–3 orders of magnitude faster than other tested tools with similar accuracy. We validate the performance of the method for fold and superfamily assignment in a large benchmark set of protein structures. We finally provide a series of examples to illustrate the usefulness of this method and its application in biological discovery. Conclusions The method is able to detect partial structure matching, rigid body shifts, conformational changes and tolerates substantial structural variation arising from insertions, deletions and sequence divergence, as well as structural convergence of unrelated proteins.Abstract Background The total number of known three-dimensional protein structures is rapidly increasing. Consequently, the need for fast structural search against complete databases without a significant loss of accuracy is increasingly demanding. Recently, TopSearch, an ultra-fast method for finding rigid structural relationships between a query structure and the complete Protein Data Bank (PDB), at the multi-chain level, has been released. However, comparable accurate flexible structural aligners to perform efficient whole database searches of multi-domain proteins are not yet available. The availability of such a tool is critical for a sustainable boosting of biological discovery. Results Here we report on the development of a new method for the fast and flexible comparison of protein structure chains. The method relies on the calculation of 2D matrices containing a description of the three-dimensional arrangement of secondary structure elements (angles and distances). The comparison involves the matching of an ensemble of substructures through a nested-two-steps dynamic programming algorithm. The unique features of this new approach are the integration and trade-off balancing of the following: 1) speed, 2) accuracy and 3) global and semiglobal flexible structure alignment by integration of local substructure matching. The comparison, and matching with competitive accuracy, of one medium sized (250-aa) query structure against the complete PDB database (216,322 protein chains) takes about 8 min using an average desktop computer. The method is at least 2–3 orders of magnitude faster than other tested tools with similar accuracy. We validate the performance of the method for fold and superfamily assignment in a large benchmark set of protein structures. We finally provide a series of examples to illustrate the usefulness of this method and its application in biological discovery. Conclusions The method is able to detect partial structure matching, rigid body shifts, conformational changes and tolerates substantial structural variation arising from insertions, deletions and sequence divergence, as well as structural convergence of unrelated proteins.