On the analysis of remd protein structure prediction simulations for reducing volume of analytical data

• Ano de defesa: 2017
• Autor(a) principal: Macedo, Rafael Cauduro Oliveira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul; Escola Politécnica; Brasil; PUCRS; Programa de Pós-Graduação em Ciência da Computação
• Palavras-chave em Português: Replica Exchange Molecular Dynamics; Protein Structure Prediction; Filtering; Quality Metric; Predição de Estruturas de Proteínas; Filtragem; Métrica de Qualidade; CIENCIA DA COMPUTACAO::TEORIA DA COMPUTACAO
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/8268

Proteins perform a vital role in all living beings, mediating a series of processes necessary to life. Although we have ways to determine the composition of such molecules, we lack sufficient knowledge regarding the determination of their 3D structure in a cheap and fast manner, which plays an important role in their functions. One of the main computational methods applied to the study of proteins and their folding process, which determine its structure, is Molecular Dynamics. An enhancement of this method, known as Replica-Exchange Molecular Dynamics (or REMD) is capable of producing much better results, at the expense of a significant increase in computational costs and volume of raw data generated. This dissertation presents a novel optimization for this method, titled Analytical Data Filtering, which aims to optimize post-simulation analysis by filtering unsatisfactory predicted structures via the use of different absolute quality metrics. The proposed methodology has the potential of working together with other optimization approaches as well as covering an area still untouched at large by them to the best of the author knowledge. Further on, the SnapFi tool is presented, a tool designed specially for the purpose of filtering unsatisfactory structure predictions and also being able to work with the different optimization approaches of the Replica-Exchange Molecular Dynamics method. A study was then conducted on a test dataset of REMD protein structure prediction simulations aiming to elucidate a series of formulated hypothesis regarding the impact of the different temperatures of the REMD process in the final quality of the predicted structures, the efficiency of the different absolute quality metrics and a possible filtering configuration that take advantage of such metrics. It was observed that high temperatures may be safely discarded from post-simulation analysis of REMD protein structure prediction simulations, that absolute quality metrics posses a high variance of efficiency (regarding quality terms) between different protein structure prediction simulations and that different filtering configurations composed of such quality metrics carry on this inconvenient variance.