Computational Three-Residue Fragment Assembly and Folding Optimization for Protein Structure Design

Abstract

Computational modeling of the unique tertiary structure of a protein from its amino acid sequence alone is one of the important challenges in science and technology. The tertiary structure itself and the folding mechanism toward it are indispensable for understanding the function and the biological role of the protein. One of the computational methods often used for this modeling is the fragment assembly method because it shows good structural modeling performance in many cases. There are limitations, however, in the conventional fragment assembly methods. Arguments for uses of energy functions and global optimization to predict the structures are in progress, for example. In this study, a new modeling method to predict protein tertiary structures is proposed. The proposed system mainly consists of two methods. The first one is a fragment assembly, in which 3-residue fragments of representative protein chains are used to produce prototypes of a given sequence of amino acids. The second one is global optimization, which uses folding optimization to construct final protein structures. One of our computational models of the protein, which yielded a 5.15 A root mean square deviation for its native tertiary structure, is provided with other experiments.