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In addition to the genetic message, DNA base sequence carries a multitude of structural and energetic signals related to its biological packaging and processing. These codes govern how the double-helical molecule deforms in response to proteins and other ligands and when and where the genetic information is expressed. DNA is not just a passive substrate of cellular proteins but an active player with physical properties capable of influencing the three-dimensional organization of genetic sequences and the activity of regulatory proteins and processing enzymes. Understanding the pathways and capabilities of DNA deformation is thus crucial for deciphering the codes behind the regulation, organization, and dynamics of various genomes. Acquiring this knowledge requires a systematic view of the structural landscapes accessible to DNA as it deforms in solution and adjusts to interactions with other molecules. This information, in turn, offers reliable benchmarks for predictions of nucleic acid interactions and structures.
The available high-resolution structures of DNA — both free and bound to proteins, drugs, and other ligands — constitute a rich resource for characterizing DNA geometries and deformations. Double-helical structures are conventionally characterized by a wide variety of conformational parameters, including (i) the identities and lengths of the non-covalent hydrogen bonds between complementary (Watson-Crick) base pairs, (ii) the puckering of the sugar rings, (iii) the values of the torsion angles along the sugar-phosphate backbone and the glycosyl torsion between the sugar and base, (iv) the magnitudes of the intra- and inter-strand distances and angles between selected atoms (P···P, C1´···C1´, etc.), (v) the values of rigid-body parameters that describe the spatial arrangements of interacting bases and successive base pairs, both in a local frame and in a global helical frame, (vi) the positions of the phosphate groups with respect to the bases and base pairs, (vii) the degree of overlap between stacked bases and base pairs, (viii) the widths of the minor and major grooves, etc. The 3DNA suite of programs developed in our laboratory determines these and other conformational information from the coordinates of any DNA-containing structure [1-3].
3DNALandscapes is a new database for exploring the conformational features of DNA. The database has been designed to study DNA backbone, sugar-base side group, base-pair, base-pair-step, and complementary-strand arrangements statistically, using 3DNA-derived information across multiple structures in combination with other currently available data resources, such as structural classifications and descriptions found in the Protein Data Bank (PDB)  and Nucleic Acid Database (NDB) . The database contains all currently available DNA-containing structures deposited in the PDB, including the complete sets of models reported for many X-ray and NMR structures. The data are stored in a rational schema that organizes tables of information in a hierarchical fashion. The highest level of the schema contains basic structural information, such as conformational classifications, sequences, and resolution. The next level divides the data into two categories: base pairing and base-pair-step information. The lowest level of the schema contains the derived parameters associated with the base pairs and the base-pair steps. To date, the database comprises 6,192 structural models, 73,983 base pairs, and 68,155 base-pair steps. Each of the base pairs and base-pair steps is characterized by approximately 40 derived parameters.
We have constructed a web interface (http://3dnascapes.rutgers.edu) to link, report, plot, and analyze the structural parameters in the aforementioned database. Its main component is a search function that enables the user to collect structural data and statistical results in a step-wise manner. First, the user must choose a set of structures by specifying the experimental method, binding information etc. or by listing a set of PDB identifiers. The user next selects the type of the structural information — e.g., hydrogen bonds, torsions, base-pair step parameters, etc. — to be included in the report. Finally, the user sees (i) a grid-view table listing all parameter entries, which can be exported as a data file, (ii) a gallery of histogram plots of the tabulated parameters, and (iii) basic statistical information grouped by base/nucleotide, base-pair or base-pair-step type. Each entry in the grid-view table contains a link to a context page with detailed 3D spatial and sequential information about the specific base, base pair or base-pair step. The web interface also includes a tutorial on the search functionalities and a page with technical definitions of the parameters stored in the database.
The PDB and NDB contain a number of derived conformational parameters, including the base-pair and base-pair-step parameters obtained with 3DNA. Although these databases include some of the information stored in the DNALandscapes database, not all of the information is contained in either of them. Also, the PDB and NDB are designed to be structure-centric, meaning that data from a single structure are easy to obtain. Gathering data for a specific parameter or parameter set across multiple nucleic acid structures is difficult or impossible with these interfaces. The information collected in the DNALandscapes database provides insights into the intrinsic sequence-dependent structure and deformability of DNA as well as useful benchmarks for the analysis and simulation of other DNA structures.
1. Olson, W. K., Lu, X.-J. (2003) 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids. Res. 31(17): 5108-5121.
2. Lu X-J. and Olson W.K. (2008) 3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three dimensional nucleic-acid structures, Nature Protocols 3(7): 1213-1227
3. Zheng, G., Lu, X-J., Olson W.K. (2009), Web 3DNA - a web server for the analysis, reconstruction, and visualization of three-dimensional nucleic-acid structures, Nucleic Acids Res., 37(Web Server issue): W240-W246.
4. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Res. 28(1): 235-242.
5. Berman, H. M., Olson, W. K., Beveridge, D. L., Westbrook, J., Gelbin, A., Demeny, T., Hsieh, S.-H., Srinivasan, A. R., and Schneider, B. (1992) The Nucleic Acid Database. A Comprehensive relational database of three-dimensional structures of nucleic acids. Biophys. J. 63(3) 751-759.