About DRV

 

The sequence specific DNA recognition by proteins is mainly driven by two different but strongly connected procedures, called base (or direct) and shape (or indirect) readout. Base readout mechanisms are established by the chemical recognition of molecular patterns located in the bottom of the major and minor grooves of DNA.  Shape readout mechanisms involve DNA specificity determining properties whose influence on sequence specific interaction is not achieved by direct chemical mechanisms but rather by defining less obvious components promoting or compromising the steric connection of the interacting partners. Two characteristic examples for features affecting the shape readout of DNA are the flexibility and the stability of the double helix.

 

DNA Readout Viewer (DRV) is a free on-line service developed by the Bioinformatics Group of the Biological Research Centre of Hungarian Academy of Sciences (Szeged, Hungary), providing novel and intuitive representation methods for visualisation of the base and shape readout features of sequence specific DNA-protein interactions. DRV displays the base readout features according to the chemical functional groups of the DNA grooves (FGDR, Functional Group DNA Representation) while shape readout features are visualised based on di or trinucleotide parameters (PCD, Physico-chemical and Conformational Descriptors) using an organized colour scale format. Technically DRV is a client-server software with three separate modules displaying the DNA recognition event from three distinct aspects. DNA Plotter, the first of the three visualising modules of DRV, provides a comprehensive view about the direct and indirect specificity determining features of native DNA. The Motif Plotter tool displays the base readout information of agglomerative binding site descriptions like PFMs (Position Frequency Matrix) by using a novel functional group based representation. The third module, Interface Plotter, combines the visualisation elements of DNA plotter with the available 3D structural information from PDB database, and projects the DNA-protein contact interface hydrogen bonding pattern of the 3D structure to a simplified 2D chemical functional group texture of the DNA major and minor grooves. In addition, Interface Plotter module provides realistic 3D views preconfigured for the visualisation of functional elements participating in the establishment of DNA-protein contact interfaces. DRV primarily approaches the DNA recognition problem from the DNA's point of view so the major part of the visualisation efforts is focusing on the DNA molecule, and the protein partner mostly appears only in the textual supplementary information.

 

The functional group based DNA representation implemented in DRV is only suitable for displaying DNA double helices with regular B or A double stranded conformation. The Interface plotter module of DRV is based on a local database of nucleo-protein contact interface structures compatible with the FGDR concept. All data entries of the DRV database are originated from those nucleo-protein structures of PDB databank that passed a filtering process for FGDR compatibility. For example, those structures where the nucleic acid partner was RNA, or the double strandness was compromised for some reason were excluded from DRV database. The current version of DRV structure database contains 2155 DNA-protein interfaces, generated by filtering out the non-DRV compatible members from the set of 4250 PDB entries containing nucleo-protein structures.

 

 

 

 

DRV application examples

 

The DRV service utilises novel visualisation concepts, helping the researchers to recognise and comprehend the specificity determining components of DNA-protein contact interfaces remaining obscured in the traditional nucleotide-based DNA representation.  Among others the DNA plotter tool can be used for detecting the identical functional group positions in different sequences (Fig.1) while the Motif plotter module can help identifying conserved functional groups in the ambiguous DNA motifs of protein binding sites (Fig. 2). The Interface plotter function of DRV allows the user to have a simplified schematic view on the hydrogen bonding pattern along with the physicochemical and conformational parameter fingerprint of DNA segments recognised by DNA binding proteins and also provides a realistic 3D structural view about these DNA-protein contact interfaces (Fig. 3).

 

 

Fig.1. Identical functional groups in different sequences

 

 

Fig. 2. Conserved functional groups in STAT1 binding sites

 

 

Fig. 3. DNA-protein contact interface of the Lex repressor DNA complex (PDB: 3jso)