Estudo estrutural e de propriedades de reconhecimento receptor-ligante dos alvos IKK1, IKK2 e MAPKp38 utilizando técnicas de modelagem molecular

• Ano de defesa: 2011
• Autor(a) principal: Guedes, Isabella Alvim
• Orientador(a): Dardenne, Laurent Emmanuel
• Banca de defesa: Sant'anna, Carlos Maurício Rabello de , Nicolás, Marisa Fabiana , Fraga, Carlos Alberto Manssour
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Laboratório Nacional de Computação Científica
• Programa de Pós-Graduação: Programa de Pós-Graduação em Modelagem Computacional
• Departamento: Coordenação de Pós-Graduação e Aperfeiçoamento (COPGA)
• País: BR
• Palavras-chave em Português: Estrutura molecular
• Palavras-chave em Inglês: Molecular structure
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
• Link de acesso: https://tede.lncc.br/handle/tede/155

The protein kinases are responsible for regulating various biological mechanisms. The active protein kinase can phosphorylate several substrates and proteins in the body, having an important role in regulating biological functions. The lack of phosphorylation in the process of this family of proteins is associated with various diseases such as cancer, diabetes and rheumatoid arthritis. The human genome contains approximately 478 different kinase genes. Among these, the protein kinases IKK-2 and MAPKp38 are considered potential targets for developing anti-inflammatory drugs. In this work, we used the techniques of comparative modeling and molecular docking for a better understanding of the molecular characteristics and properties which can confer potency and selectivity to the inhibitors described in the literature for these two enzymes. The three-dimensional models built for the IKK's (1 and 2) made possible the understanding of special features available in these enzymes. The study of molecular docking with inhibitors allowed to infer important information about the characteristics of the binding modes that give potency and selectivity to the compounds tested. Regarding MAPKp38, cross-docking studies showed that the conformational change of the A-loop of this enzyme has a profound influence on the results of molecular docking of the inhibitors tested. The success rates of sets of structures of the enzyme were estimated, in order to indicate the combinations of structures that could achieve greater accuracy in real ensemble docking experiments.