Protein Structure Prediction : Model Building and Quality Assessment

Proteins play a crucial roll in all biological processes. The wide range of protein functions is made possible through the many different conformations that the protein chain can adopt. The structure of a protein is extremely important for its function, but to determine the structure of protein experimentally is both difficult and time consuming. In fact with the current methods it is not possible to study all the billions of proteins in the world by experiments. Hence, for the vast majority of proteins the only way to get structural information is through the use of a method that predicts the structure of a protein based on the amino acid sequence. This thesis focuses on improving the current protein structure prediction methods by combining different prediction approaches together with machine-learning techniques. This work has resulted in some of the best automatic servers in world – Pcons and Pmodeller. As a part of the improvement of our automatic servers, I have also developed one of the best methods for predicting the quality of a protein model – ProQ. In addition, I have also developed methods to predict the local quality of a protein, based on the structure – ProQres and based on evolutionary information – ProQprof. Finally, I have also performed the first large-scale benchmark of publicly available homology modeling programs