Estimation of distribution algorithms for ab initio protein structure prediction

Author(s)

Daniel Rodrigo Ferraz Bonetti

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Matemáticas e de Computação (ICMC/SB)
• Defense date: 2015-03-05

Examining board members

Alexandre Cláudio Botazzo Delbem; Myriam Regattieri de Biase da Silva Delgado; Jochen Einbeck; Paulo Sérgio Lopes de Oliveira; Fernando Luis Barroso da Silva

• Advisor: Alexandre Cláudio Botazzo Delbem

Abstract

Proteins are molecules that perform critical roles in the living organism and they are essential for their lifes. To understand the function of a protein, its 3D structure should be known. However, to find the protein structure is an expensive and a time-consuming task, requiring highly skilled professionals. Aiming to overcome such a limitation, computational methods for Protein Structure Prediction (PSP) have been investigated, in order to predict the protein structure from its amino acid sequence. Most of computational methods require knowledge from already determined structures from experimental methods in order to predict an unknown protein. Although computational methods such as Rosetta, I-Tasser and Quark have showed success in their predictions, they are only capable to predict quite similar structures to already known proteins obtained experimentally. The use of such a prior knowledge in the predictions of Rosetta, I-Tasser and Quark may lead to biased predictions. In order to develop a computational algorithm for PSP free of bias, we developed an Estimation of Distribution Algorithm applied to PSP with full-atom and ab initio model. A computational algorithm with ab initio model is mainly interesting when dealing with proteins with low similarity with the known proteins. In this work, we developed an Estimation of Distribution Algorithm with three probabilistic models: univariate, bivariate and hierarchical. The univariate deals with multi-modality of the distribution of the data of a single variable. The bivariate treats the dihedral angles (Proteins are molecules that perform critical roles in the living organism and they are essential for their lifes. To understand the function of a protein, its 3D structure should be known. However, to find the protein structure is an expensive and a time-consuming task, requiring highly skilled professionals. Aiming to overcome such a limitation, computational methods for Protein Structure Prediction (PSP) have been investigated, in order to predict the protein structure from its amino acid sequence. Most of computational methods require knowledge from already determined structures from experimental methods in order to predict an unknown protein. Although computational methods such as Rosetta, I-Tasser and Quark have showed success in their predictions, they are only capable to predict quite similar structures to already known proteins obtained experimentally. The use of such a prior knowledge in the predictions of Rosetta, I-Tasser and Quark may lead to biased predictions. In order to develop a computational algorithm for PSP free of bias, we developed an Estimation of Distribution Algorithm applied to PSP with full-atom and ab initio model. A computational algorithm with ab initio model is mainly interesting when dealing with proteins with low similarity with the known proteins. In this work, we developed an Estimation of Distribution Algorithm with three probabilistic models: univariate, bivariate and hierarchical. The univariate deals with multi-modality of the distribution of the data of a single variable. The bivariate treats the dihedral angles (Φ Ψ) within an amino acid as correlated variables. The hierarchical approach splits the original problem into subproblems and attempts to treat these problems in a separated manner. The experiments show that, indeed, it is possible to achieve better results when modeling the correlation (Φ Ψ). The hierarchical model also showed that is possible to improve the quality of results, mainly for proteins above 50 residues. Besides, we compared our proposed techniques among other metaheuristics from literatures such as: Random Walk, Monte Carlo, Genetic Algorithm and Differential Evolution. The results show that even a less efficient metaheuristic such as Random Walk managed to find the correct structure, however using many prior knowledge (prediction that may be biased). On the other hand, our proposed EDA for PSP was able to find the correct structure with no prior knowledge at all, so we can call this prediction as pure ab initio (biased-free). (AU)

• FAPESP's process: 10/02928-2 - Estimation of distributed algorithms for ab initio prediction of protein structures
• Grantee: Daniel Rodrigo Ferraz Bonetti
• Support Opportunities: Scholarships in Brazil - Doctorate