β-Bulges: Extensive structural analyses of β-sheets irregularities

beta-Sheets are quite frequent in protein structures and are stabilized by regular main-chain hydrogen bond patterns. Irregularities in -sheets, named -bulges, are distorted regions between two consecutive hydrogen bonds. They disrupt the classical alternation of side chain direction and can alter the directionality of -strands. They are implicated in protein-protein interactions and are introduced to avoid -strand aggregation. Five different types of -bulges are defined. Previous studies on -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 -bulge distribution and conservation in terms of local backbone conformations and amino acid composition. Our dataset consists of 66 times more -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 -bulges are preferably localized at the N- and C-termini of -strands, but contrary to the earlier studies, no significant conservation of -bulges was observed among structural homologues. Displacement of -bulges along the sequence was also investigated by Molecular Dynamics simulations.