RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures

Abstract

Background: Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization.

Description: RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available at http://rnafrabase.cs.put.poznan.pl.

Conclusions: RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field.

Figure 1

Data flow in RNA FRABASE 2.0. The overall data encoding idea that underpins RNA FRABASE 2.0 (illustrated by the sections of the diagram in orange) is based on the information deposited in PDB and NDB (shown by the cylinder in blue), our own scripts and external applications (denoted by the rectangles in yellow). The search algorithms output a broad range of structural information (represented by the parallelograms in turquioise).

Figure 2

An example of the RNA secondary structure which includes residues with missing coordinates (2A64). The figure illustrates a graphic image of the secondary structure (top), the sequence (middle) and dot-bracket representation of the secondary structure (bottom) for he 2A64 RNA molecule. The residues missing from the PDB file coordinate section are marked in red.

Figure 3

Accession to the database of RNA secondary structures given in dot-bracket and graphic format. Here we see a range of RNA FRABASE 2.0 interface snapshots concerning "Secondary structures" menu. Panel A shows the front page window, Panel B illustrates the 'Details' window for the selected structure and Panel C represents a visualization of the selected secondary structure model.

Figure 4

Example loop structures stored in RNA FRABASE 2.0 database. Each residue within the RNA loop is represented by a circle. Different shades of gray enable us to distinguish between single strands within the same loop. Two circles connected by a double line represent a closing base pair.

Figure 5

Example of the use of the wildcard characters "^" and "$" in the query. The figure shows two example structures: (a) RNA duplex and (b) tRNA acceptor stem. The input pattern used to run search algorithm and the number of matching fragments are provided for each example. Residues, base pairs and strands are marked by employing the same convention as that used in Figure 4.

Figure 6

The influence of the strand shift operation on 3D fragment search results. The figure illustrates the search for the RNA three-way junction (a). It is defined by the input pattern shown in section (b) which differs when the strand shift operation is disabled (c) or enabled (d). If the strand shift is enabled, then the RNA FRABASE engine searches for fragments which match with one of the three patterns shown in (d).

Figure 7

RNA FRABASE 2.0 interface snapshots concerning the "Search" menu. Panel A shows the front page window. Panel B enables 'Advanced search' facilities with the provided filters. Panel C illustrates a list of query-matching RNA fragments with related structural information. Panel D highlights the Jmol visualization of the selected fragment. Panels E, F and G are the windows for 'Atom coordinates', 'Torsion angles' and 'Base pairs' for the selected fragment, respectively.