Computational Identification and Design of Complementary β-Strand Sequences.

The ß-sheet is a regular secondary structure element which consists of linear segments called ß-strands. They are involved in many important biological processes, and some are known to be related to serious diseases such as neurologic disorders and amyloidosis. The self-assembly of ß-sheet peptides also has practical applications in material sciences since they can be building blocks of repeated nanostructures. Therefore, computational algorithms for identification of ß-sheet formation can offer useful insight into the mechanism of disease-prone protein segments and the construction of biocompatible nanomaterials. Despite the recent advances in structure-based methods for the assessment of atomic interactions, identifying amyloidogenic peptides has proven to be extremely difficult since they are structurally very flexible. Thus, an alternative strategy is required to describe ß-sheet formation. It has been hypothesized and observed that there are certain amino acid propensities between ß-strand pairs. Based on this hypothesis, a database search algorithm, B-SIDER, is developed for the identification and design of ß-sheet forming sequences. Given a target sequence, the algorithm identifies exact or partial matches from the structure database and constructs a position-specific score matrix. The score matrix can be utilized to design novel sequences that can form a ß-sheet specifically with the target.