Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina
Ano de defesa: | 2016 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Biologia Celular e Molecular
|
Departamento: |
Faculdade de Bioci?ncias
|
País: |
Brasil
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.pucrs.br/tede2/handle/tede/7146 |
Resumo: | Cyclin-dependent kinases (CDKs) comprise an interesting biological system for development of docking protocols and scoring functions, due to the abundance of complexed structures for which binding affinity data is available. Here, we report application of an integrated computational approach to carry out docking against a data set composed of 176 structures of CDK in complex with inhibitors. To our knowledge, this is the largest data set of CDK crystallographic structures submitted to molecular docking simulation. Our results indicate that the proposed strategy for docking against CDKs generates poses with docking root-mean square deviation below 2.0 ? for most of the structures in the data set. In addition, we describe the development of scoring functions tailored to CDKs. Statistical analysis of pre-docking and re-docking results, using the proposed scoring functions for CDKs, indicates that these functions are able to predict affinity with better performance when compared with previously reported benchmarks for CDKs. |
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Azevedo Junior, Walter Filgueira de085.019.058-44http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723433Y4061.336.869-01http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4247722P3Levin, Nayara Maria Bernhardt2017-03-07T18:02:43Z2016-12-16http://tede2.pucrs.br/tede2/handle/tede/7146Cyclin-dependent kinases (CDKs) comprise an interesting biological system for development of docking protocols and scoring functions, due to the abundance of complexed structures for which binding affinity data is available. Here, we report application of an integrated computational approach to carry out docking against a data set composed of 176 structures of CDK in complex with inhibitors. To our knowledge, this is the largest data set of CDK crystallographic structures submitted to molecular docking simulation. Our results indicate that the proposed strategy for docking against CDKs generates poses with docking root-mean square deviation below 2.0 ? for most of the structures in the data set. In addition, we describe the development of scoring functions tailored to CDKs. Statistical analysis of pre-docking and re-docking results, using the proposed scoring functions for CDKs, indicates that these functions are able to predict affinity with better performance when compared with previously reported benchmarks for CDKs.Quinases dependentes de ciclina (CDKs) s?o sistemas biol?gicos de interesse para o desenvolvimento de protocolos de docking e fun??es escore, devido ? abund?ncia de estruturas cristalogr?ficas complexadas para as quais h? disponibilidade de dados de afinidade de liga??o. Neste trabalho relatamos a aplica??o de uma abordagem computacional integrada para realizar o docking molecular em um conjunto de dados composto por 176 estruturas cristalogr?ficas de CDK em complexo com inibidores. De nosso conhecimento, este ? o maior conjunto de dados de estruturas cristalogr?ficas de CDKs utilizado para simula??o de docking molecular. Nossos resultados indicam que a estrat?gia proposta para docking de CDKs gera poses com desvio m?dio quadr?tico abaixo de 2,0 ? para a maioria das estruturas do conjunto de dados. Al?m disso, descrevemos o desenvolvimento das fun??es escore adaptados ?s CDKs. A an?lise estat?stica dos resultados de pr?-docking e re-docking, empregando as fun??es escore propostas para CDKs, indica que estas fun??es s?o capazes de prever afinidade com o melhor desempenho quando comparado com as fun??es previamente relatadas para CDKs.Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2017-03-07T18:02:42Z No. of bitstreams: 1 DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf: 2253906 bytes, checksum: 347d5947bf640845e7934a922c486c79 (MD5)Made available in DSpace on 2017-03-07T18:02:43Z (GMT). No. of bitstreams: 1 DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf: 2253906 bytes, checksum: 347d5947bf640845e7934a922c486c79 (MD5) Previous issue date: 2016-12-16Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/167362/DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Biologia Celular e MolecularPUCRSBrasilFaculdade de Bioci?nciasQUINASES CICLINA-DEPENDENTESCICLO CELULARBIOLOGIA MOLECULARCIENCIAS BIOLOGICAS::BIOLOGIA GERALEstudo computacional da intera??o de inibidores com quinases dependentes de ciclinainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis819824693009663736060060060060036528317262667714-16345593859312446972075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.jpgDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.jpgimage/jpeg3493http://tede2.pucrs.br/tede2/bitstream/tede/7146/5/DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.jpg15b2abd6f491c85daf2f59f8b54cb580MD55TEXTDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.txtDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.txttext/plain63725http://tede2.pucrs.br/tede2/bitstream/tede/7146/4/DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf.txtf6a9c9ee18fffabea9cea5b2a546bdcbMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-8610http://tede2.pucrs.br/tede2/bitstream/tede/7146/3/license.txt5a9d6006225b368ef605ba16b4f6d1beMD53ORIGINALDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdfDIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdfapplication/pdf2253906http://tede2.pucrs.br/tede2/bitstream/tede/7146/2/DIS_NAYARA_MARIA_BERNHARDT_LEVIN_COMPLETO.pdf347d5947bf640845e7934a922c486c79MD52tede/71462017-03-07 20:00:52.161oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2017-03-07T23:00:52Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
title |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
spellingShingle |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina Levin, Nayara Maria Bernhardt QUINASES CICLINA-DEPENDENTES CICLO CELULAR BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
title_full |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
title_fullStr |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
title_full_unstemmed |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
title_sort |
Estudo computacional da intera??o de inibidores com quinases dependentes de ciclina |
author |
Levin, Nayara Maria Bernhardt |
author_facet |
Levin, Nayara Maria Bernhardt |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Azevedo Junior, Walter Filgueira de |
dc.contributor.advisor1ID.fl_str_mv |
085.019.058-44 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723433Y4 |
dc.contributor.authorID.fl_str_mv |
061.336.869-01 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4247722P3 |
dc.contributor.author.fl_str_mv |
Levin, Nayara Maria Bernhardt |
contributor_str_mv |
Azevedo Junior, Walter Filgueira de |
dc.subject.por.fl_str_mv |
QUINASES CICLINA-DEPENDENTES CICLO CELULAR BIOLOGIA MOLECULAR |
topic |
QUINASES CICLINA-DEPENDENTES CICLO CELULAR BIOLOGIA MOLECULAR CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Cyclin-dependent kinases (CDKs) comprise an interesting biological system for development of docking protocols and scoring functions, due to the abundance of complexed structures for which binding affinity data is available. Here, we report application of an integrated computational approach to carry out docking against a data set composed of 176 structures of CDK in complex with inhibitors. To our knowledge, this is the largest data set of CDK crystallographic structures submitted to molecular docking simulation. Our results indicate that the proposed strategy for docking against CDKs generates poses with docking root-mean square deviation below 2.0 ? for most of the structures in the data set. In addition, we describe the development of scoring functions tailored to CDKs. Statistical analysis of pre-docking and re-docking results, using the proposed scoring functions for CDKs, indicates that these functions are able to predict affinity with better performance when compared with previously reported benchmarks for CDKs. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-12-16 |
dc.date.accessioned.fl_str_mv |
2017-03-07T18:02:43Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
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http://tede2.pucrs.br/tede2/handle/tede/7146 |
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http://tede2.pucrs.br/tede2/handle/tede/7146 |
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por |
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por |
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8198246930096637360 |
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600 600 600 600 |
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36528317262667714 |
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-1634559385931244697 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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Programa de P?s-Gradua??o em Biologia Celular e Molecular |
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PUCRS |
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Faculdade de Bioci?ncias |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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