MapTurns: mapping the structure, H-bonding, and contexts of beta turns in proteins

Abstract

Motivation: Beta turns are the most common type of secondary structure in proteins after alpha helices and beta sheets and play many key structural and functional roles. Turn backbone (BB) geometry has been classified at multiple levels of precision, but the current picture of side chain (SC) structure and interaction in turns is incomplete, because the distribution of SC conformations associated with each sequence motif has commonly been represented only by a static image of a single, typical structure for each turn BB geometry, and only motifs which specify a single amino acid (e.g. aspartic acid at turn position 1) have been systematically investigated. Furthermore, no general evaluation has been made of the SC interactions between turns and their BB neighborhoods. Finally, the visualization and comparison of the wide range of turn conformations has been hampered by the almost exclusive characterization of turn structure in BB dihedral-angle (Ramachandran) space.

Results: This work introduces MapTurns, a web server for motif maps, which employ a turn-local Euclidean-space coordinate system and a global turn alignment to comprehensively map the distributions of BB and SC structure and H-bonding associated with sequence motifs in beta turns and their local BB contexts. Maps characterize many new SC motifs, provide detailed rationalizations of sequence preferences, and support mutational analysis and the general study of SC interactions, and they should prove useful in applications such as protein design.

Availability and implementation: MapTurns is available at www.betaturn.com. Sample code is available at: https://github.com/nenewell/MapTurns/tree/main.

Figure 1.

Upper-level motif map screen for the sequence motif that specifies Asp at turn position 3 and Ser just after the turn (D3S + 1). The upper-level motif map screen supports the exploration of the recurrent BB and SC structures and H-bonds associated with a sequence motif in beta turns. BB and SC clusters are represented by their medoids, which are color-coded with a heatmap of relative motif statistical significance (for BB clusters, at left, with the selected cluster highlighted) or cluster size (for the SC clusters within the selected BB cluster, at right) and scaled according to cluster size. Navigation is achieved via menus that order clusters by statistical significance (for BB clusters) or cluster size (for SC clusters, in which all members contain the sequence motif), and motif statistics are provided, along with text annotations for a selection of key motifs. In the figure, the D3S + 1 motif’s most significant BB cluster is selected along with its largest SC cluster, and the SC cluster viewer at right shows that these choices are associated with SC/SC and SC/BB H-bonds linking the turn to the bulge in the common type 1 beta-bulge loop (Milner-White 1987). The lower-level screen, opened by the button above the SC cluster viewer, supports the navigation of the “tail” clusters (contexts) associated with the sequence motif within the BB cluster selected on the upper-level screen, as well as the browsing and profiling of the underlying PDB structures.