ExploreTurns: A web tool for the exploration, analysis, and classification of beta turns and structured loops in proteins; application to beta-bulge and Schellman loops, Asx helix caps, beta hairpins and other hydrogen-bonded motifs

Abstract

The most common type of protein secondary structure after the alpha helix and beta strand is the beta turn, in which the backbone (BB) chain abruptly changes direction over four amino acid residues. Existing tools for the study of beta turns characterize their structures exclusively in the Ramachandran space of BB dihedral angles, which presents challenges for the visualization, comparison and analysis of the wide variety of turn geometries. A recent study has introduced a turn-local Euclidean-space coordinate system and a global alignment for turns, along with a set of geometric parameters for their bulk BB shape which describe modes of structural variation not explicitly captured by Ramachandran-space systems. These features, and others, are incorporated here into ExploreTurns, a tool specialized for the exploration, analysis, geometric tuning and retrieval of beta turns and their local contexts which combines the advantages of Ramachandran- and Euclidean-space representations. ExploreTurns is a database selection screen, structure profiler and 3D viewer, integrated onto a single web page, that renders a redundancy-screened, PDB-derived beta-turn dataset structurally addressable by a wide range of criteria describing the turns and their BB neighborhoods. The tool is applied here to a proposed generalization of the beta-bulge loop, a mapping of helix-capping sequence preferences, a conformational profile of the Schellman loop, and an analysis of the depth dependence of turn geometry, and it should prove generally useful in research, education, and applications such as protein design, in which an enhanced Euclidean-space description of turns and structural tuning may improve performance.

A geometric parameterization for beta turns

“…The turn-local coordinate system and global alignment derived here resolve the difficulties with visualization inherent in the Ramachandran-space turn representation, providing a natural framework for the comparison and analysis of the wide variety of beta-turn structures and the contexts in which they occur, including H-bonded motifs, ligand-binding/active sites and supersecondary structures. The utility of this framework has been demonstrated by the application of ExploreTurns to the detection and characterization of multiple new short H-bonded loops, the mapping of sequence preferences in Asx N-caps, and the profiling of Schellman loop/beta turn combinations 5 .…”

“…Three beta-turn classification systems developed in previous studies are employed in this work; each partitions turns by BB geometry in Ramachandran space at a different level of precision. These systems, summarized in the ExploreTurns 5 online help at www.betaturn.com, are referred to here, in order of increasing precision, as the “classical” type system, finalized by Hutchinson and Thornton 6 , and the BB cluster and Ramachandran type systems, both derived by Shapovalov et al 4 , with the last system based on the map of Ramachandran space due to Hollingsworth and Karplus 7 . Beta turns exhibit a wide range of BB conformations which, taken together with the variety of intra- and extra-turn structural interactions that their side-chains (SCs) can mediate, enable them to play crucial roles in multiple contexts in proteins; for an overview, see Roles of beta turns in proteins at www.betaturn.com.…”

“…Three beta-turn classification systems developed in previous studies are employed in this work; each partitions turns by BB geometry in Ramachandran space at a different level of precision. These systems, summarized in the ExploreTurns 6 online help at www.betaturn.com, are referred to here, in order of increasing precision, as the “classical” type system 7,8,9,10 and the BB cluster and Ramachandran type systems 4 , with the last system based on the map of Ramachandran space due to Hollingsworth and Karplus 11 .…”

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

“…Motifs that are important in particular turn contexts, such as H-bonded structures (e.g. beta-hairpins 11 , beta-bulge loops 12,13 , alpha-beta loops 14 , helix caps 15,16 ) or supersecondary structures in which a turn connects helices/strands, can be identified with the ExploreTurns 13 tool, also available at www.betaturn.com.…”

“…Motifs that are important in particular turn contexts, such as H-bonded structures (e.g. beta-hairpins 10 , beta-bulge loops 11,12 , alpha-beta loops 13 , helix caps 14,15 ) or supersecondary structures in which a turn connects two elements of repetitive structure, can be identified with ExploreTurns 12 , a separate tool, also available at www.betaturn.com, which supports the comprehensive exploration, analysis, geometric tuning and retrieval of beta turns and the motifs that include them.…”