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dc.contributor.advisorAcevedo Sarmiento, Orlando Emiliospa
dc.contributor.authorPineda Agudelo, Cynthia Dajanna
dc.coverage.spatialCampus UMNGspa
dc.date.accessioned2019-09-12T20:08:16Z
dc.date.accessioned2019-12-26T21:08:49Z
dc.date.available2019-09-12T20:08:16Z
dc.date.available2019-12-26T21:08:49Z
dc.date.issued2019-07-16
dc.identifier.urihttp://hdl.handle.net/10654/32111
dc.description.abstractInhibir un factor de transcripción que interviene en la producción de proteínas relacionadas con vías de transducción de señales en células cancerígenas se ha estudiado desde hace varios años para la terapia contra el cáncer. El Factor de choque térmico HSF1 es uno de los blancos moleculares prometedores en este tipo de investigaciones. HSF1 regula la expresión de proteínas Hsps implicadas en el plegamiento, crecimiento celular, diferenciación, respuesta al estrés y vías apoptoticas; está presente en las células en su forma monomerica inactiva pero a partir de estímulos como el estrés fisiológico producido por UV, choque térmico y quimioterapia; se trimeriza, iniciando la transcripción de las Hsps, las cuales se unen a proteínas mal plegadas, generando resistencia a la muerte celular inducida en tratamientos anticancerígenos. Hemos realizado análisis computacionales de la interacción entre el sitio de unión con el DNA de HSF1 y los flavonoides Rutina y quercetina. Con el objetivo de encontrar candidatos a inhibidores de la transcripción de HSF1, para ser usados como coadyuvantes en los tratamientos contra el cáncer.spa
dc.description.tableofcontents1. ABSTRACT 4 2. RESUMEN 5 3. JUSTIFICACIÓN 8 4. INTRODUCCION 11 5. MARCO TEORICO 11 5.1. CANCER 11 5.1.1 Generalidades 11 5.1.2 Causas 12 5.1.3 Panorama mundial 12 5.1.4 Panorama en Colombia 13 5.1.5 Tratamiento 13 6. PROTEINAS DE CHOQUE TERMICO 13 6.1 Hsps y enfermedades 15 6.2 FACTORES DE CHOQUE TERMICO (HSF) 16 6.2.1 Factor de choque térmico HSF1 17 6.2.1.1. Estructura del gen HSF1 18 6.2.1.2. Asociacones con cáncer 19 6.2.1.3 Inhibición de HSF1 19 7. FLAVONOIDES 21 7.1 Quercetina 23 7.1.1. Generalidades 23 7.1.2. Actividad inhibidora 27 7.2. Rutina 28 7.2.1. Generalidades 28 7.2.2. Actividad como inhibidora 29 8. DISEÑO DE FARMACOS POR COMPUTADOR (Computer assisted molecular design) 30 9. MODELAMIENTO MOLECULAR 31 9.1. Mecánica cuántica 31 9.2. Mecánica molecular 31 9.2.1. MMFF94 32 9.2.2. Método de Monte Carlo 33 9.2.3. Dinámica molecular 35 9.3. Métodos de minimización de energía 35 9.3.1. Algoritmos sin uso de derivadas 35 10. MODELAMIENTO DE PROTEINAS 37 10.1. Perfil de hidrofobicidad 38 10.2. Mapa de Ramachandran 39 11. ACOPLAMIENTO MOLECULAR (Molecular Docking) 40 11.1. Generalidades 40 11.2. Evaluación de la interacción proteína-ligando 41 11.2.1. Funciones de Scoring 42 12. OBJETIVOS 47 12.1. Objetivo General 47 12.2. Objetivos Específicos 47 13. PREGUNTA DE INVESTIGACIÓN: 47 14. PROBLEMA DE INVESTIGACIÓN. 47 15. METODOLOGIA 47 15.1. Software: 47 15.2. Recursos Web: 48 15.3. Procedimiento (Preparación del receptor y el ligando) 48 15.3.1. Preparación del Receptor 48 15.3.2. Estructura del Receptor 48 16. ANALISIS DE RESULTADOS 49 16.1. Preparación del Receptor y ligandos. 50 16.1.1. Preparación del Receptor (proteína blanco) 50 16.1.2. Preparación de ligandos. 61 16.2. Docking Molecular 64 16.2.1. Resultados Molecular Docking de 2DLU y Quercetina 67 16.2.2. Aminoácidos relevantes del docking Molecular de 2LDU-QUE y 2LDU-RUT de menor energía. 71 16.2.3. Resultados comparativos de los ligados evaluados. 72 17. Conclusiones 74 18. Infografía 75 II. Interacción Receptor Ligando (HSF-Quercetina) 78 III. Bibliografía 103spa
dc.format.mimetypeapplication/pdfspa
dc.language.isospaspa
dc.rightsDerechos Reservados - Universidad Militar Nueva Granada, 2019spa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.5/co/spa
dc.titleModelo de la interacción entre rutina (3-Rhamno-glucoside de quercentina) y factor de choque térmico HSF1 humanospa
dc.typeinfo:eu-repo/semantics/bachelorThesisspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.subject.lembFLAVONOIDESspa
dc.subject.lembCANCER - ASPECTOS MOLECULARESspa
dc.publisher.departmentFacultad de Ciencias Básicasspa
dc.type.localTrabajo de gradospa
dc.description.abstractenglishInhibiting a transcription factor involved in the production of proteins related to signal transduction pathways in cancer cells has been studied for many years. The heat shock factor HSF1 is one of the promising molecular targets in this type of research. In fact, HSF1 regulates expression of Hsps proteins involved in folding, cell growth, differentiation, stress response and apoptosis pathways. HSF1 is present in cells in an inactive monomeric form; In stress response caused by UV the heat shock factor 1 is trimerized, transcription of Hsps is initiated, and binding of heat shock proteins to the misfolded proteins starts, the HSF1 activation generates resistance in the cell death mechanisms in anticancer treatments. We have carried out computational analysis of the interaction model between the binding DNA site of HSF1 and two flavonoids (Quercetin and rutin). With the objective of evaluate in silico the binging affinity of this components and propose one of them as a potential inhibitor model of HSF1 transcription, for use as an adjuvant in cancer treatments.eng
dc.title.translatedModel of interaction between (3-Rhamno-glucoside of quercetin) and human head shock factor HSF1spa
dc.subject.keywordsMolecular dockingspa
dc.subject.keywordsMolecular modelingspa
dc.subject.keywordsFlavonoidspa
dc.publisher.programBiología Aplicadaspa
dc.creator.degreenameBiólogospa
dc.description.degreelevelPregradospa
dc.publisher.facultyCiencias Básicas - Biología Aplicadaspa
dc.type.dcmi-type-vocabularyTextspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dc.rights.creativecommonsAtribución-NoComercial-SinDerivadasspa
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dc.subject.proposalMolecular dockingspa
dc.subject.proposalModelamiento molecularspa
dc.subject.proposalFlavonoidesspa
dc.publisher.grantorUniversidad Militar Nueva Granadaspa


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