Web 3DNA 2.0 and G.A pairs in RNA folding

[xiangjun]

Two papers closely related to 3DNA/DSSR have recently been published, as shown below:

• "Web 3DNA 2.0 for the analysis, visualization, and modeling of 3D nucleic acid structures" in Nucleic Acids Research (NAR). Here is the abstract, including a graphical illustration.
  

  Web 3DNA (w3DNA) 2.0 is a significantly enhanced version of the widely used w3DNA server for the analysis, visualization, and modeling of 3D nucleic-acid-containing structures. Since its initial release in 2009, the w3DNA server has continuously served the community by making commonly-used features of the 3DNA suite of command-line programs readily accessible. However, due to the lack of updates, w3DNA has clearly shown its age in terms of modern web technologies and it has long lagged behind further developments of 3DNA per se. The w3DNA 2.0 server presented here overcomes all known shortcomings of w3DNA while maintaining its battle-tested characteristics. Technically, w3DNA 2.0 implements a simple and intuitive interface (with sensible defaults) for increased usability, and it complies with HTML5 web standards for broad accessibility. Featurewise, w3DNA 2.0 employs the most recent version of 3DNA, enhanced with many new functionalities, including: the automatic handling of modified nucleotides; a set of ‘simple’ base-pair and step parameters for qualitative characterization of non-Watson–Crick double- helical structures; new structural parameters that integrate the rigid base plane and the backbone phosphate group, the two nucleic acid components most reliably determined with X-ray crystallography; in silico base mutations that preserve the backbone geometry; and a notably improved module for building models of single-stranded RNA, double- helical DNA, Pauling triplex, G-quadruplex, or DNA structures ‘decorated’ with proteins. The w3DNA 2.0 server is freely available, without registration, at http://web.x3dna.org.

  
  
  
  Notably, details for reproducing our reported results (figures and tables) are available in a dedicated section "web 3DNA 2.0 (http://web.x3dna.org)" on the 3DNA Forum.

• "Effects of Noncanonical Base Pairing on RNA Folding: Structural Context and Spatial Arrangements of G·A Pairs" in ACS Biochemistry. Here is the abstract with a graphical illustration.
  

  Noncanonical base pairs play important roles in assembling the three-dimensional structures critical to the diverse functions of RNA. These associations contribute to the looped segments that intersperse the canonical double-helical elements within folded, globular RNA molecules. They stitch together various structural elements, serve as recognition elements for other molecules, and act as sites of intrinsic stiffness or deformability. This work takes advantage of new software (DSSR) designed to streamline the analysis and annotation of RNA three-dimensional structures. The multiscale structural information gathered for individual molecules, combined with the growing number of unique, well-resolved RNA structures, makes it possible to examine the collective features deeply and to uncover previously unrecognized patterns of chain organization. Here we focus on a subset of noncanonical base pairs involving guanine and adenine and the links between their modes of association, secondary structural context, and contributions to tertiary folding. The rigorous descriptions of base-pair geometry that we employ facilitate characterization of recurrent geometric motifs and the structural settings in which these arrangements occur. Moreover, the numerical parameters hint at the natural motions of the interacting bases and the pathways likely to connect different spatial forms. We draw attention to higher-order multiplexes involving two or more G·A pairs and the roles these associations appear to play in bridging different secondary structural units. The collective data reveal pairing propensities in base organization, secondary structural context, and deformability and serve as a starting point for further multiscale investigations and/or simulations of RNA folding.

  
  
  
  The paper includes a paragraph in the discussion section on differences between 3DNA/DSSR and the well-established LW (Leontis-Westhof) scheme:
  
  

  Qualitative descriptions of noncanonical RNA base pairing, pioneered by Leontis and Westhof^9,41 and linked in this work to the rigid-body parameters of interacting bases, have proven valuable in deciphering the connections between RNA primary, secondary, and tertiary structures. The present categorization is based on the positions of the hydrogen-bonded atoms with respect to a standard, embedded base reference frame³⁰ defined in terms of an idealized Watson−Crick base pair. The major- and minor-groove base edges used here correspond in most cases to what are termed the Hoogsteen and sugar edges in the Leontis−Westhof scheme (one can compare the two classification schemes in Table S2). The + and − symbols introduced in 3DNA²⁴ and DSSR²⁷ unambiguously distinguish the relative orientations of the two bases. The trans and cis designations used in the earlier literature, however, are qualitative in nature and often uncertain. There are many “nc” (near cis, as in ncWW) and “nt” (near trans, as in ntSH) annotations listed in the RNA Structure Atlas; see, for example, the base-pair interactions in the sarcin−ricin domain of E. coli 23S rRNA found by entering PDB entry 1msy at http://rna.bgsu.edu/rna3dhub/pdb. The assignment of qualitative descriptors of RNA associations on the basis of atomic identity alone is generally not clear-cut. Numerical differences in the rigid-body parameters are critical to differentiating pairing schemes that share a common hydrogen bond, e.g., the G(N3)···A(N6) interaction found in m−W_II and m−M_I arrangements of G and A (Table 1 and Figures 4 and S3). The numerical data also provide a basis for following conformational transitions and may potentially be of value in making functional and other meaningful distinctions among RNA base pairs.

  
  See also a recent thread Noncanonical base pair standards on the 3DNA Forum and the section titled “3.2.2 Base pairs” in the DSSR User Manual.