Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications
Ano de defesa: | 2023 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | eng |
Instituição de defesa: |
Universidade Federal de Lavras
Programa de Pós-graduação em Agroquímica UFLA brasil Departamento de Química |
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Link de acesso: | http://repositorio.ufla.br/jspui/handle/1/56746 |
Resumo: | Alzheimer's disease (AD) affects a large part of the world population, with social and economic impacts. One of the etiological hypotheses proposes that there is a link between AD and type 2 diabetes mellitus (T2DM), even though the mechanism is yet to be unraveled. Studies show that vanadium complexes, such as the BMOV and VO(metf)2·H2O, are potential agents against this neurodegenerative disorder. Thus, Molecular Dynamics (MD) simulations are advantageous for obtaining information about the structures and interactions of these complexes with the biological targets involved in the process, namely AMPK and PTP1B. However, DMs are dependent on the choice of a good force field. Therefore, the present work aims to develop AMBER force field parameters for BMOV and VO(metf)2·H2O, since the literature lacks such information on metal complexes. From quantum-mechanical calculations, the global minimum energy structures were found, with theory level B3LYP/def2-TZVP plus ECP for the vanadium atom. RESP charges and Hessian matrix calculations were performed using the same functional and basis set. The values of force constants were obtained by diagonalizing the Hessian matrix and the Lennard-Jones parameters were assigned based on GAFF, for all atoms except vanadium. In order to validate the developed force fields, MD simulations in vacuum and room temperature were carried out. After that, MDs were performed in order to acquire information about relevant interactions between vanadium complexes and the proteins associated to AD. The new models developed and reported by this work showed to be efficient to describe the molecules under study, when compared to experimental data and to quantum references. Furthermore, great insights about the behavior of the systems, such as relevant residues that interact with BMOV and VO(metf)2·H2O are reported. It is expected that this work may assist to motivate future work involving vanadium complexes for the treatment AD. |
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Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applicationsSondando interações entre complexos de vanádio e alvos em potencial para o tratamento de Alzheimer: parametrização de um novo campo de força amber e aplicações biológicasComplexos de vanádioCampo de força AMBERDinâmica molecularDocking molecularDoença de AlzheimerVanadium complexesAMBER force fieldMolecular dynamicsMolecular dockingAlzheimer’s diseaseQuímicaAlzheimer's disease (AD) affects a large part of the world population, with social and economic impacts. One of the etiological hypotheses proposes that there is a link between AD and type 2 diabetes mellitus (T2DM), even though the mechanism is yet to be unraveled. Studies show that vanadium complexes, such as the BMOV and VO(metf)2·H2O, are potential agents against this neurodegenerative disorder. Thus, Molecular Dynamics (MD) simulations are advantageous for obtaining information about the structures and interactions of these complexes with the biological targets involved in the process, namely AMPK and PTP1B. However, DMs are dependent on the choice of a good force field. Therefore, the present work aims to develop AMBER force field parameters for BMOV and VO(metf)2·H2O, since the literature lacks such information on metal complexes. From quantum-mechanical calculations, the global minimum energy structures were found, with theory level B3LYP/def2-TZVP plus ECP for the vanadium atom. RESP charges and Hessian matrix calculations were performed using the same functional and basis set. The values of force constants were obtained by diagonalizing the Hessian matrix and the Lennard-Jones parameters were assigned based on GAFF, for all atoms except vanadium. In order to validate the developed force fields, MD simulations in vacuum and room temperature were carried out. After that, MDs were performed in order to acquire information about relevant interactions between vanadium complexes and the proteins associated to AD. The new models developed and reported by this work showed to be efficient to describe the molecules under study, when compared to experimental data and to quantum references. Furthermore, great insights about the behavior of the systems, such as relevant residues that interact with BMOV and VO(metf)2·H2O are reported. It is expected that this work may assist to motivate future work involving vanadium complexes for the treatment AD.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A doença de Alzheimer (DA) afeta uma grande parte da população mundial, com impactos sociais e econômicos. Uma das hipóteses etiológicas propõe que existe uma ligação entre DA e diabetes mellitus tipo 2 (DMT2), embora o mecanismo ainda não tenha sido desvendado. Estudos mostram que complexos de vanádio, como o BMOV e o VO(metf)2·H2O, são agentes potenciais contra este distúrbio neurodegenerativo. Dessa forma, as simulações de Dinâmica Molecular (DM) são vantajosas para obter informações sobre a estrutura e interação destes complexos com os alvos biológicos envolvidos no processo, nesse caso, AMPK e PTP1B. Entretanto, as DMs dependem da escolha de bons campos de forças. Portanto, o presente trabalho visa desenvolver parâmetros de campo de força AMBER para BMOV e VO(metf)2·H2O, uma vez que a literatura carece de tais informações sobre complexos metálicos. A partir de cálculos quanto-mecânicos, foram encontradas estruturas com mínimos de energia global, empregando o nível de teoria B3LYP/def2-TZVP mais ECP para o átomo de vanádio. As cargas RESP e os cálculos da matriz de Hessiana foram realizados usando os mesmos funcional e função de base. Os valores das constantes de força foram obtidos através da diagonalização da matriz de Hessiana e os parâmetros de Lennard-Jones foram atribuídos com base no GAFF, para todos os átomos, exceto vanádio. A fim de validar os campos de força desenvolvidos, foram realizadas simulações de DM no vácuo e em temperatura ambiente. Depois disso, foram realizados cálculos de DMs a fim de adquirir informações sobre as interações relevantes entre os complexos de vanádio e as proteínas associadas a estas duas condições. Os novos modelos desenvolvidos e relatados por este trabalho se mostraram eficientes para descrever as moléculas sob estudo, quando comparadas aos dados experimentais e as referências quânticas. Além disso, grandes insights sobre o comportamento dos sistemas, tais como resíduos relevantes que interagem com BMOV e VO(metf)2·H2O são relatados. Espera-se que este trabalho possa ajudar a motivar trabalhos futuros envolvendo complexos de vanádio para o tratamento DA.Universidade Federal de LavrasPrograma de Pós-graduação em AgroquímicaUFLAbrasilDepartamento de QuímicaCunha, Elaine Fontes Ferreira daRamalho, Teodorico de CastroAquino, Adélia Justina AguiarBatista, Ana Paula de LimaCaetano, Melissa SoaresCanuto, Sylvio Roberto AcciolyTavares, Camila Assis2023-05-03T18:51:23Z2023-05-03T18:51:23Z2023-05-032023-02-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfTAVARES, C. A. Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications. 2023. 166 p. Tese (Doutorado em Agroquímica)–Universidade Federal de Lavras, Lavras, 2023.http://repositorio.ufla.br/jspui/handle/1/56746engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFLAinstname:Universidade Federal de Lavras (UFLA)instacron:UFLA2023-05-04T12:22:47Zoai:localhost:1/56746Repositório InstitucionalPUBhttp://repositorio.ufla.br/oai/requestnivaldo@ufla.br || repositorio.biblioteca@ufla.bropendoar:2023-05-04T12:22:47Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA)false |
dc.title.none.fl_str_mv |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications Sondando interações entre complexos de vanádio e alvos em potencial para o tratamento de Alzheimer: parametrização de um novo campo de força amber e aplicações biológicas |
title |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
spellingShingle |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications Tavares, Camila Assis Complexos de vanádio Campo de força AMBER Dinâmica molecular Docking molecular Doença de Alzheimer Vanadium complexes AMBER force field Molecular dynamics Molecular docking Alzheimer’s disease Química |
title_short |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
title_full |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
title_fullStr |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
title_full_unstemmed |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
title_sort |
Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications |
author |
Tavares, Camila Assis |
author_facet |
Tavares, Camila Assis |
author_role |
author |
dc.contributor.none.fl_str_mv |
Cunha, Elaine Fontes Ferreira da Ramalho, Teodorico de Castro Aquino, Adélia Justina Aguiar Batista, Ana Paula de Lima Caetano, Melissa Soares Canuto, Sylvio Roberto Accioly |
dc.contributor.author.fl_str_mv |
Tavares, Camila Assis |
dc.subject.por.fl_str_mv |
Complexos de vanádio Campo de força AMBER Dinâmica molecular Docking molecular Doença de Alzheimer Vanadium complexes AMBER force field Molecular dynamics Molecular docking Alzheimer’s disease Química |
topic |
Complexos de vanádio Campo de força AMBER Dinâmica molecular Docking molecular Doença de Alzheimer Vanadium complexes AMBER force field Molecular dynamics Molecular docking Alzheimer’s disease Química |
description |
Alzheimer's disease (AD) affects a large part of the world population, with social and economic impacts. One of the etiological hypotheses proposes that there is a link between AD and type 2 diabetes mellitus (T2DM), even though the mechanism is yet to be unraveled. Studies show that vanadium complexes, such as the BMOV and VO(metf)2·H2O, are potential agents against this neurodegenerative disorder. Thus, Molecular Dynamics (MD) simulations are advantageous for obtaining information about the structures and interactions of these complexes with the biological targets involved in the process, namely AMPK and PTP1B. However, DMs are dependent on the choice of a good force field. Therefore, the present work aims to develop AMBER force field parameters for BMOV and VO(metf)2·H2O, since the literature lacks such information on metal complexes. From quantum-mechanical calculations, the global minimum energy structures were found, with theory level B3LYP/def2-TZVP plus ECP for the vanadium atom. RESP charges and Hessian matrix calculations were performed using the same functional and basis set. The values of force constants were obtained by diagonalizing the Hessian matrix and the Lennard-Jones parameters were assigned based on GAFF, for all atoms except vanadium. In order to validate the developed force fields, MD simulations in vacuum and room temperature were carried out. After that, MDs were performed in order to acquire information about relevant interactions between vanadium complexes and the proteins associated to AD. The new models developed and reported by this work showed to be efficient to describe the molecules under study, when compared to experimental data and to quantum references. Furthermore, great insights about the behavior of the systems, such as relevant residues that interact with BMOV and VO(metf)2·H2O are reported. It is expected that this work may assist to motivate future work involving vanadium complexes for the treatment AD. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-05-03T18:51:23Z 2023-05-03T18:51:23Z 2023-05-03 2023-02-24 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
TAVARES, C. A. Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications. 2023. 166 p. Tese (Doutorado em Agroquímica)–Universidade Federal de Lavras, Lavras, 2023. http://repositorio.ufla.br/jspui/handle/1/56746 |
identifier_str_mv |
TAVARES, C. A. Probing interactions between vanadium complexes and potential targets for Alzheimer's treatment: parameterization of a new amber force field and biological applications. 2023. 166 p. Tese (Doutorado em Agroquímica)–Universidade Federal de Lavras, Lavras, 2023. |
url |
http://repositorio.ufla.br/jspui/handle/1/56746 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Lavras Programa de Pós-graduação em Agroquímica UFLA brasil Departamento de Química |
publisher.none.fl_str_mv |
Universidade Federal de Lavras Programa de Pós-graduação em Agroquímica UFLA brasil Departamento de Química |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFLA instname:Universidade Federal de Lavras (UFLA) instacron:UFLA |
instname_str |
Universidade Federal de Lavras (UFLA) |
instacron_str |
UFLA |
institution |
UFLA |
reponame_str |
Repositório Institucional da UFLA |
collection |
Repositório Institucional da UFLA |
repository.name.fl_str_mv |
Repositório Institucional da UFLA - Universidade Federal de Lavras (UFLA) |
repository.mail.fl_str_mv |
nivaldo@ufla.br || repositorio.biblioteca@ufla.br |
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1784549841886511104 |