Predição de estruturas de proteínas utilizando restrições de RMN e um modelo coarse grained

• Ano de defesa: 2014
• Autor(a) principal: Werdt, Paulo Roberto Teixeira
• Orientador(a): Dardenne, Laurent Emmanuel
• Banca de defesa: Barbosa, Helio José Corrêa , Pascutti, Pedro Geraldo
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Laboratório Nacional de Computação Cientifica
• 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: Biologia molecular; Processamento eletrônico de dados; Algorítmos genéticos
• Palavras-chave em Inglês: Molecular biology
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
• Link de acesso: https://tede.lncc.br/handle/tede/185

The prediction of the three-dimensional structure of proteins (PSP) has been one of the most challenging fields of computational biology, both for its applicability in the field of medicine and drug design, as for its high complexity and computational cost. The main objective of this work was to implement and investigate the predictive potential in the context of the program GAPF (Genetic Algorithm for Protein Folding), the use of a Coarse Grained (CG) model, coupled with a genetic algorithm of multiple minimum, designed specifically to predict protein structures, using restraints of distance and angles obtained from experiments of Nuclear Magnetic Resonance (NMR). A second objective was, using structures determined by NMR and deposited in the Protein Data Bank (PDB), to identify, classify and generate statistics of those NMR restraints that might be more relevant in a process of predicting protein structures. In this sense, programs were developed, in C++ language, to read, interpret, analyze and engage the NMR information contained in the PDB files, making it possible to use the restraints contained in these files, by the program GAPF. A visualization program was also developed, using the OpenGL library, which allows the observation of protein structures with their respective NMR restraints. Simulations were performed on a test group of ten proteins with known structure, and the results were compared with those obtained using an all atom model. The results obtained with the use of the CG model were equivalent or, in most cases, exceeded the results achieved with the all atom force field. Besides allowing a significant reduction in computational cost, the use of the CG model enabled a significant reduction of the number of NMR restraints necessary for the prediction of a structure with a folding considered correct or satisfactory.