Desenvolvimento de estratégias para o uso de mapa de contatos em problemas de predição de novo de estruturas de proteínas

• Autor(a) principal: Santos, Karina Baptista dos
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações do LNCC
• Texto Completo: https://tede.lncc.br/handle/tede/355
• topic: Proteínas; Predição de estruturas de proteínas; Algoritmo genético; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Abstract Protein structure prediction is one of the most important problems in computational molecular biology and aims to determine the three dimensional structure of proteins solely from the amino acid sequence. Since 1994, the state of the art of protein structure prediction (PSP) methods has been assessed in the CASP events (The Critical Assessment of Techniques for Protein Structure Prediction), and the methodological improvements have been remarkable. During the last three CASP editions (10th, 11th, and 12th), promising results were achieved with the introduction of co-evolution information, in the form of residues contact maps, in methodologies for PSP. The goals of this work are to carry out an assessment of the information given by contact maps and to develop a strategy to use the contact constraints from these maps to improve the quality of the predicted models in a de novo PSP approach. A residue-residue potential, with information from contact maps, is proposed in the form of distance constraints. This potential is added to the fitness function of the GAPF program, which predicts protein structures using a genetic algorithm with phenotypic crowding in a free-modeling approach. Two contact maps were generated to evaluate the potential developed here: (i) a native contact map obtained directly from the experimental structure and, (ii) predicted contact maps by MetaPSICOV and RaptorX-Contact. The experiments performed indicate that the contact potential implemented in the GAPF program promoted an important improvement in the accuracy of the predictions. For example, it was possible to obtain models with a reduction of up to 7.32Å for RMSD and 35.28% in GDT-TS for the best protein model predicted for target T0820-D1, when comparing with the values obtained for standard version of the GAPF program using the same number of evaluations. The comparison with consolidated PSP methods in the literature, such as Quark and Rosetta, has shown that by using the contact strategies proposed in this work, GAPF became a good candidate for de novo protein structure predictions. These results confirm the use of contact maps as a useful strategy for de novo PSP methodologies.