A systematic analysis of the beta hairpin motif in the Protein Data Bank

Abstract

The beta hairpin motif is a ubiquitous protein structural motif that can be found in molecules across the tree of life. This motif, which is also popular in synthetically designed proteins and peptides, is known for its stability and adaptability to broad functions. Here, we systematically probe all 49,000 unique beta hairpin substructures contained within the Protein Data Bank (PDB) to uncover key characteristics correlated with stable beta hairpin structure, including amino acid biases and enriched interstrand contacts. We find that position specific amino acid preferences, while seen throughout the beta hairpin structure, are most evident within the turn region, where they depend on subtle turn dynamics associated with turn length and secondary structure. We also establish a set of broad design principles, such as the inclusion of aspartic acid residues at a specific position and the careful consideration of desired secondary structure when selecting residues for the turn region, that can be applied to the generation of libraries encoding proteins or peptides containing beta hairpin structures.

A Perspective on the (Rise and Fall of) Protein β-Turns

“…They are distributed in an impressive number of different folds, such as the β-hairpin repeat proteins [ 65 ]. A very large number of β-turns is found in β-hairpins [ 66 ], but some are without [ 67 ], and a number of β-turns are not found in β-hairpins. It is critical to note that this connecting loop resembles a hairpin and it is logical that β-turns are found inside (as for γ- and α-turns too [ 66 ]), but it is not systematic.…”

Current Approaches in Supersecondary Structures Investigation

“…In our studies, we have also shown the high stability of SSS for 4 types of helical pairs accessed by the MD [15][16][17]. The β-hairpin motif is also characterized by high autonomous stability, which makes this motif popular for producing artificial protein structures with desired properties (hydrogels, antimicrobial peptides) [52][53][54][55].…”

Designing and identifying β-hairpin peptide macrocycles with antibiotic potential

“…Our design scheme leveraged our recently completed systematic analysis of more than 49,000 β-hairpin motifs in the Protein Data Bank. This analysis identified position-specific amino acid preferences in the strand and turn regions ( 14 ). Using this information, we designed two ribosomally encoded 20–amino acid cyclic β-hairpin peptide libraries ( Fig.…”