β-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in β-sheets, named β-bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of β-strands. They are implicated in protein-protein interactions and are introduced to avoid β-strand aggregation. Five different types of β-bulges are defined. Previous studies on β-bulges were performed on a limited number of protein structures or one specific family. These studies evoked a potential conservation during evolution. In this work, we analyze the β-bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more β-bulges than the last systematic study (Chan et al. Protein Science 1993, 2:1574-1590). Novel amino acid preferences are underlined and local structure conformations are highlighted by the use of a structural alphabet. We observed that β-bulges are preferably localized at the N- and C-termini of β-strands, but contrary to the earlier studies, no significant conservation of β-bulges was observed among structural homologues. Displacement of β-bulges along the sequence was also investigated by Molecular Dynamics simulations.
Keywords: beta-sheets; beta-strand; evolution; folds; mining; protein blocks; protein structure; structural alphabet; structural comparison; structural irregularity.
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