TOPS: an enhanced database of protein structural topology

Abstract

The TOPS database holds topological descriptions of protein structures. These compact and highly abstract descriptions reduce the protein fold to a sequence of Secondary Structure Elements (SSEs) and three sets of pairwise relationships between them, hydrogen bonds relating parallel and anti- parallel beta strands, spatial adjacencies relating neighbouring SSEs, and the chiralities of selected supersecondary structures, including connections in betaalphabeta units and between parallel alpha helices. The database is used as a resource for visualizing folding topologies, fast topological pattern searching and structure comparison. Here, significant enhancements to the TOPS database are described. The topological description has been enhanced to include packing relationships between helices, which significantly improves the description of protein folds with little beta strand content. Further, the topological description has been annotated with sequence information. The query interfaces to the database have been improved and the new version can be found at http://www.tops.leeds.ac.uk/.

Figure 1

Topological representations of protein structures consider a sequence of SSEs, i.e. helices (circles) or strands (triangles), together with relationships like spatial adjacency within the fold and approximate orientation, neglecting details like the lengths of SSEs and loops. (A) A 2D TOPS cartoon for of 1ra9 (dihydrofolate reductase). TOPS cartoons are pseudo-2D schematic abstractions, where the third dimension is implied, since SSEs are considered to have an approximate direction of ‘up’ or ‘down’ (connecting lines drawn to the centre of the symbol indicate connection to the top, and those drawn to the edge indicate connection to the base). Direction information for strands is duplicated, upward pointing triangles indicating ‘up’ strands and vice versa. Adjacent strand pairs are connected by H-bonds, being parallel or anti-parallel. Chiralities between parallel strands are also implicit. (B) A TOPS diagram of 1ra9. Hydrogen bonds and supersecondary chiralities are shown explicitly (parallel in red, anti-parallel in green, right-handed chiralities in blue).