Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol

61 páginas : gráficas

Autores:: Valencia Rodríguez, Catherine

Tipo de recurso:: Trabajo de grado de pregrado

Fecha de publicación:: 2018

Institución:: Universidad de Ciencias Aplicadas y Ambientales U.D.C.A

Repositorio:: Repositorio Institucional UDCA

Idioma:: spa

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dc.title.spa.fl_str_mv	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
title	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
spellingShingle	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol Dinámica molecular -- Investigaciones Alquilfenol -- Investigaciones Química XIAP Dominio BIR3 Apoptosis celular Cáncer DIFAC Acoplamiento molecular
title_short	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
title_full	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
title_fullStr	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
title_full_unstemmed	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
title_sort	Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol
dc.creator.fl_str_mv	Valencia Rodríguez, Catherine
dc.contributor.advisor.spa.fl_str_mv	Ortíz Verano, Ismael, dir.
dc.contributor.author.spa.fl_str_mv	Valencia Rodríguez, Catherine
dc.subject.lemb.spa.fl_str_mv	Dinámica molecular -- Investigaciones Alquilfenol -- Investigaciones Química
topic	Dinámica molecular -- Investigaciones Alquilfenol -- Investigaciones Química XIAP Dominio BIR3 Apoptosis celular Cáncer DIFAC Acoplamiento molecular
dc.subject.proposal.spa.fl_str_mv	XIAP Dominio BIR3 Apoptosis celular Cáncer DIFAC Acoplamiento molecular
description	61 páginas : gráficas
publishDate	2018
dc.date.accessioned.spa.fl_str_mv	2018-09-05T19:39:43Z
dc.date.available.spa.fl_str_mv	2018-09-05T19:39:43Z
dc.date.issued.spa.fl_str_mv	2018
dc.type.spa.fl_str_mv	Trabajo de grado - Pregrado
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dc.relation.references.spa.fl_str_mv	A. M. Verhagen and Vaux D. L. Cell death regulation by the mammalian IAP antagonist Diablo/Smac. Apoptosis, 7(2):163–166, 2002. M. Hemshekhar, M. Sebastin Santhosh, K. Kemparaju, and K. S. Girish. Emerging roles of anacardic acid and its derivatives: A pharmacological overview. Basic & Clinical Pharmacology & Toxicology, 110(2):122–132, 2012. OMS. la Organizaci´on Mundial de la Salud. Divisi´on de Informaci´on de la Organizaci´on Mundial de la Salud. World Health Organization. et al. Global action plan for the prevention and control of noncommunicable diseases 2013-2020. 2013. J. A. DiMasi, R. W. Hansen, and H. G. Grabowski. The price of innovation: new estimates of drug development costs. Journal of Health Economics, 22(2):151–185, 2003. W. J. Geldenhuys, K. E. Gaasch, M. Watson, D.D. Allen, and C. J. Van der Schyf. Optimizing the use of open-source software applications in drug discovery. Drug Discovery Today, 11(3):127–132, 2006. M. Hern´andez. Estudio te´orico de acoplamiento molecular de alquil benzoquinosnas y alquil fenoles con el dominio BIR3 de la proteina XIAP. PhD thesis, Universidad de Ciencias Aplicadas y Ambientales, 2015. J. Orjala, P. Mian, T. Rali, and O. Sticher. Gibbilimbols A- D, Cytotoxic and antibacterial alkenylphenols from Piper gibbilimbum. Journal of Natural Products, 61(7):939–941, 1998 S. M. Srinivasula, R. Hegde, A. Saleh, P. Datta, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature, 410(6824):112, 2001 D. M. Mu˜noz and L.M Cuca. Compuestos citot´oxicos de origen vegetal y su relaci´on con prote´ınas inhibidoras de apoptosis (IAP). Revista Colombiana de Cancerolog´ıa, 20(3):124–134, 2016. I. Guerrero, L. Cuellar, L. M Taxa, R. Mej´ıa, M. J Alvarez, M. Zaharia Bassan, R. Pizarro, C. L. Santos, and J. C. Mari´ategui. Genes reguladores de apopt´osis y proliferaci´on celular en mujeres vih positivo y c´ancer de cuello uterino. Acta Cancerol, 33(1):28–34, 2005 B. Ling, L. Dong, R. Zhang, Z. Wang, Y. Liu, and C. Liu. Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics. Journal of Molecular Graphics and Modelling, 29(3):354–362, 2010. D. Voet and J. G. Voet. Bioqu´ımica. Ed. M´edica Panamericana, 2006. R. F. Pellizzon. Pesquisa na ´area da sa´ude: 1. base de dados DeCS (Descritores em Ci´encias da sa´ude). Acta Cir´urgica Brasileira, 2004. B. Zhang, Z. Nikolovska, Y. Zhang, L. Bai, S. Qiu, C. Y. Yang, H. Sun, S. Wang, and Y. Wu. Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of caspases. Journal of Medicinal Chemistry, 51(23):7352–7355, 2008 D. Barna and ChemAxon. Marvinsketch, 1998-2017 J. C. Shelley, A. Cholleti, L. L. Frye, J. R. Greenwood, M. R. Timlin, and M. Uchimaya. Epik: a software program for pKa prediction and protonation state generation for druglike molecules. Journal of Computer-aided Molecular Design, 21(12):681–691, 2007. The Scripps Research Institute. Autodock, 1989-2017. G. Cuevas, F. Cuevas, and F. Cort´es. Introducci´on a la qu´ımica computacional. Fondo de Cultura Econ´omica,, 2003. P. W Atkins and J. De Paula. Atkins qu´ımica f´ısica. M´edica Panamericana, 2008. H. M. Marques and K. L. Brown. Molecular mechanics and molecular dynamics simulations of porphyrins, metalloporphyrins, heme proteins and cobalt corrinoids. Coordination Chemistry Reviews, 225(1):123–158, 2002. M. S. P´erez. Mec´anica molecular. Monograf´ıas de la Real Academia Nacional de Farmacia, 1994. L. Jaillet, S. Artemova, and S. Redon. Im-uff: extending the universal force field for interactive molecular modeling. Journal of Molecular Graphics and Modelling, 2017. J. L. Medina, F. Lopez, and R. Castillo. Dise˜no de f´armacos asistido por computadora. Educaci´on Qu´ımica, 17(4):452–457, 2006. ] J. L. Medina, E. Fern´andez de Gortari, and J. J. Naveja. Avances en el dise˜no de f´armacos asistido por computadora. Educaci´on Qu´ımica, 26(3):180–186, 2015. Princeton Review (Firm). MCAT General Chemistry Review. Princeton Review, 2010. M. W. King. Integrative Medical Biochemistry: Examination and Board Review. McGraw Hill Professional, 2014. L. K. Cuanalo, S. Merino, and T. Scior. ¿Qu´e sabe ud. acerca de... cribado virtual? Revista Mexicana de Ciencias Farmac´euticas, 42(2):54–55, 2011. Schr¨odinger. Maestro 2016,, 2016. W. E. H. Forli, S. Halliday, R. Belew, and A. J. Olson. Autodock version 4.2. M. T. Degiacomi and M. Dal Peraro. Macromolecular symmetric assembly prediction using swarm intelligence dynamic modeling. Structure, 21(7):1097–1106, 2013. I. N. Levine. Qu´ımica cu´antica. Pearson Educaci´on, 2001. Schr¨odinger Anaconda Channel. Pymol, 2017. Linux Mark Institute. Linux Mint Sonya 18.2, Diciembre 2016. F. C. Bernstein, T. F. Koetzle, Graheme J.B., E. Meyer, M. D. Brice, J. R. Rodgers, O. Kennard, T. Shimanouchi, and M. Tasumi. The protein data bank. The FEBS Journal, 80(2):319–324, 1977. G. Wu, J. Chai, T. L Suber, W. Jia-Wei, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature, 408(6815):1008, 2000. C. Z. Nikolovska, L. Xu, Z. Hu, Y. Tomita, P. Li, P.P. Roller, R. Wang, X. Fang, R. Guo, M. Zhang, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. Journal of Medicinal Chemistry, 47(10):2430–2440, 2004
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spelling	Ortíz Verano, Ismael, dir.Valencia Rodríguez, Catherine2018-09-05T19:39:43Z2018-09-05T19:39:43Z2018https://repository.udca.edu.co/handle/11158/984QI020 V14e 201861 páginas : gráficasX-Linked Inhibitor of Apoptosis Protein (XIAP) acts as a cellular apoptosis inhibitor due to its high selectivity to caspase 9. This caspase activates caspases 3 and 7 in an autocatalytic way to produce cellular death. Alanine-Valine-Proline-Isoleucine (AVPI) join XIAPBaculovirus Inhibitor of apoptosis (BIR3) protein Repeat to inhibit selectivity to caspase 9. Recent studies evidence embelin as a powerful XIAP inhibitor. Embelin is a target in the study of low molecular mass ligands extracted from natural products, which has been used in traditional medicine. Embelin also is used as a reference compound in anti-cancer pharmaceutical products design. In this work, ligands extracted from Pipper gibbilimbum and Anarcadium occidentale were studied using molecular docking, with the autodock4.2 software package. The a nity between all the studied ligands and the BIR3 domain's active site BIR3 in XIAP was found. Also, was found that interactions in studied complexes have coincidence between 90 and 100% with interactions embelin-XIAP-BIR3. Using binding free energy and inhibition constants, better ligand-receptor complexes were predicted.Inhibidor-X de la apoptosis (XIAP) actúa como inhibidor de apoptosis celular por su alta selectividad con la caspasa 9, la cual activa de forma autocatalítica las caspasas 3 y 7 para producir muerte celular. Alanina-Valina-Prolina-Isoleucina (AVPI) se une a XIAP-Dominios repetidos IAP de baculovirus (BIR3) inhibiendo su selectividad dirigida a la caspasa 9. Estudios recientes demostraron la actividad del compuesto embelina como potente inhibidor de XIAP, convirtiéndose en un blanco de estudio los ligantes de bajo peso molecular extraídos de compuestos naturales utilizados en medicina tradicional, hacia el diseño de fármacos para el tratamiento de cáncer. En el presente trabajo se estudiaron ligantes extraídos de las plantas Piper gibbilimbum y Anarcadium occidentale, a través del acoplamiento molecular utilizando el programa autodock4.2. Se encontró afinidad de todos los ligantes con el sitio activo del dominio BIR3 de XIAP. Igualmente se determinó que los complejos encontrados tienen entre el 90% y el 100% de las interacciones en relación con embelina. En el estudio se predijo el orden de los mejores complejos ligante-receptor por medio de una evaluación de la energía libre de enlace y la constante de inhibición calculadas computacionalmente.Incluye bibliografíaPregradoQuímico(a)application/pdfspaDerechos Reservados - Universidad de Ciencias Aplicadas y Ambientaleshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenolTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/redcol/resource_type/TPhttp://purl.org/coar/version/c_970fb48d4fbd8a85Dinámica molecular -- InvestigacionesAlquilfenol -- InvestigacionesQuímicaXIAPDominio BIR3Apoptosis celularCáncerDIFACAcoplamiento molecularA. M. Verhagen and Vaux D. L. Cell death regulation by the mammalian IAP antagonist Diablo/Smac. Apoptosis, 7(2):163–166, 2002.M. Hemshekhar, M. Sebastin Santhosh, K. Kemparaju, and K. S. Girish. Emerging roles of anacardic acid and its derivatives: A pharmacological overview. Basic & Clinical Pharmacology & Toxicology, 110(2):122–132, 2012.OMS. la Organizaci´on Mundial de la Salud. Divisi´on de Informaci´on de la Organizaci´on Mundial de la Salud.World Health Organization. et al. Global action plan for the prevention and control of noncommunicable diseases 2013-2020. 2013.J. A. DiMasi, R. W. Hansen, and H. G. Grabowski. The price of innovation: new estimates of drug development costs. Journal of Health Economics, 22(2):151–185, 2003.W. J. Geldenhuys, K. E. Gaasch, M. Watson, D.D. Allen, and C. J. Van der Schyf. Optimizing the use of open-source software applications in drug discovery. Drug Discovery Today, 11(3):127–132, 2006.M. Hern´andez. Estudio te´orico de acoplamiento molecular de alquil benzoquinosnas y alquil fenoles con el dominio BIR3 de la proteina XIAP. PhD thesis, Universidad de Ciencias Aplicadas y Ambientales, 2015.J. Orjala, P. Mian, T. Rali, and O. Sticher. Gibbilimbols A- D, Cytotoxic and antibacterial alkenylphenols from Piper gibbilimbum. Journal of Natural Products, 61(7):939–941, 1998S. M. Srinivasula, R. Hegde, A. Saleh, P. Datta, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature, 410(6824):112, 2001D. M. Mu˜noz and L.M Cuca. Compuestos citot´oxicos de origen vegetal y su relaci´on con prote´ınas inhibidoras de apoptosis (IAP). Revista Colombiana de Cancerolog´ıa, 20(3):124–134, 2016.I. Guerrero, L. Cuellar, L. M Taxa, R. Mej´ıa, M. J Alvarez, M. Zaharia Bassan, R. Pizarro, C. L. Santos, and J. C. Mari´ategui. Genes reguladores de apopt´osis y proliferaci´on celular en mujeres vih positivo y c´ancer de cuello uterino. Acta Cancerol, 33(1):28–34, 2005B. Ling, L. Dong, R. Zhang, Z. Wang, Y. Liu, and C. Liu. Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics. Journal of Molecular Graphics and Modelling, 29(3):354–362, 2010.D. Voet and J. G. Voet. Bioqu´ımica. Ed. M´edica Panamericana, 2006.R. F. Pellizzon. Pesquisa na ´area da sa´ude: 1. base de dados DeCS (Descritores em Ci´encias da sa´ude). Acta Cir´urgica Brasileira, 2004.B. Zhang, Z. Nikolovska, Y. Zhang, L. Bai, S. Qiu, C. Y. Yang, H. Sun, S. Wang, and Y. Wu. Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of caspases. Journal of Medicinal Chemistry, 51(23):7352–7355, 2008D. Barna and ChemAxon. Marvinsketch, 1998-2017J. C. Shelley, A. Cholleti, L. L. Frye, J. R. Greenwood, M. R. Timlin, and M. Uchimaya. Epik: a software program for pKa prediction and protonation state generation for druglike molecules. Journal of Computer-aided Molecular Design, 21(12):681–691, 2007.The Scripps Research Institute. Autodock, 1989-2017.G. Cuevas, F. Cuevas, and F. Cort´es. Introducci´on a la qu´ımica computacional. Fondo de Cultura Econ´omica,, 2003.P. W Atkins and J. De Paula. Atkins qu´ımica f´ısica. M´edica Panamericana, 2008.H. M. Marques and K. L. Brown. Molecular mechanics and molecular dynamics simulations of porphyrins, metalloporphyrins, heme proteins and cobalt corrinoids. Coordination Chemistry Reviews, 225(1):123–158, 2002.M. S. P´erez. Mec´anica molecular. Monograf´ıas de la Real Academia Nacional de Farmacia, 1994.L. Jaillet, S. Artemova, and S. Redon. Im-uff: extending the universal force field for interactive molecular modeling. Journal of Molecular Graphics and Modelling, 2017.J. L. Medina, F. Lopez, and R. Castillo. Dise˜no de f´armacos asistido por computadora. Educaci´on Qu´ımica, 17(4):452–457, 2006.] J. L. Medina, E. Fern´andez de Gortari, and J. J. Naveja. Avances en el dise˜no de f´armacos asistido por computadora. Educaci´on Qu´ımica, 26(3):180–186, 2015.Princeton Review (Firm). MCAT General Chemistry Review. Princeton Review, 2010.M. W. King. Integrative Medical Biochemistry: Examination and Board Review. McGraw Hill Professional, 2014.L. K. Cuanalo, S. Merino, and T. Scior. ¿Qu´e sabe ud. acerca de... cribado virtual? Revista Mexicana de Ciencias Farmac´euticas, 42(2):54–55, 2011.Schr¨odinger. Maestro 2016,, 2016.W. E. H. Forli, S. Halliday, R. Belew, and A. J. Olson. Autodock version 4.2.M. T. Degiacomi and M. Dal Peraro. Macromolecular symmetric assembly prediction using swarm intelligence dynamic modeling. Structure, 21(7):1097–1106, 2013.I. N. Levine. Qu´ımica cu´antica. Pearson Educaci´on, 2001.Schr¨odinger Anaconda Channel. Pymol, 2017.Linux Mark Institute. Linux Mint Sonya 18.2, Diciembre 2016.F. C. Bernstein, T. F. Koetzle, Graheme J.B., E. Meyer, M. D. Brice, J. R. Rodgers, O. Kennard, T. Shimanouchi, and M. Tasumi. The protein data bank. The FEBS Journal, 80(2):319–324, 1977.G. Wu, J. Chai, T. L Suber, W. Jia-Wei, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature, 408(6815):1008, 2000.C. Z. Nikolovska, L. Xu, Z. Hu, Y. Tomita, P. Li, P.P. Roller, R. Wang, X. Fang, R. Guo, M. Zhang, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. Journal of Medicinal Chemistry, 47(10):2430–2440, 2004Facultad de CienciasQuímicaPublicationORIGINALTesis Catherine Valencia - 2018.pdfTesis Catherine Valencia - 2018.pdfapplication/pdf5154021https://repository.udca.edu.co/bitstreams/106a16cc-5413-4fae-ac7f-92a20ca9f9ab/download408977821901dd5c1aadd3ad3cf5bd8eMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-814775https://repository.udca.edu.co/bitstreams/7fd04f61-f036-4ef2-a37c-239eb27c0c3c/downloadf661acf14bedbf9f5d13897a0387e751MD52TEXTTesis Catherine Valencia - 2018.pdf.txtTesis Catherine Valencia - 2018.pdf.txtExtracted texttext/plain75844https://repository.udca.edu.co/bitstreams/03238ed4-8c61-409a-84b0-185a172fdaf3/download7f444d1d6cb21a4d60c8d7c224f6f8abMD53THUMBNAILTesis Catherine Valencia - 2018.pdf.jpgTesis Catherine Valencia - 2018.pdf.jpgGenerated 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en las Obras Colectivas;
b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda;
c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas.Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).
4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:
a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).
b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.
c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.
d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.
ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.
e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, Acinpro), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.
5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.
7. Término.
a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.
b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.
8. Varios.
a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.
b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.
c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.
d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.



Estudio computacional del acoplamiento molecular de XIAP-BIR3 con ligantes de núcleo estructural alquílfenol

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