The respective roles of polar/non polar binary patterns and amino acid composition in protein regular secondary structures explored exhaustively using hydrophobic cluster analysis (Proteins: Structure, Function, and Bioinformatics)

Several studies have highlighted the leading role of the sequence periodicity of polar and nonpolar amino acids (binary patterns) in the formation of regular secondary structures (RSS). However, these were based on the analysis of only a few simple cases, with no direct mean to correlate binary patterns with the limits of RSS. Here, we considered HCA-derived hydrophobic clusters (HC), which are conditioned binary patterns whose positions fit well those of RSS, and analyzed all the HC types, defined by unique binary patterns, which are commonly observed in 3D structures of globular domains. We observed that the 180 HC types with preferences for either ?-helices or ?-strands distinctly contain basic binary units typical of these RSS, a general trend thus supporting the `binary pattern preference` assumption. We also focused on HC for which observed RSS are in disagreement with their expected behavior (discordant HC). We distinguished HC types with moderate preferences for RSS, with `weak` binary patterns and versatile RSS and HC types with high preferences for RSS, with `strong` binary patterns and then displaying nonpolar amino acids at the protein surface. We show that in both cases, discordant HC can be distinguished from concordant ones by well-differentiated amino acid compositions. The obtained results could thus help to complement the currently available methods for the accurate prediction of secondary structures in proteins from the only information of a single amino acid sequence. This can be especially useful for characterizing orphan sequences and for assisting protein engineering and design. This article is protected by copyright. All rights reserved.