There are currently two consecutive standards on the nomenclature and definition of nucleic acid structural parameters, the initial 1989 Cambridge Convention, and the 1999/2001 Tsukuba Report (standard base-reference frame).
The 1989 Cambridge Convention
The 1989 EMBO Workshop (held at Cambridge, England) provided the first systemic "
definitions and nomenclature of nucleic acid structure parameters" [Dickerson
et al. (1989),
Nucleic Acids Res.,
17(5), 1797-803]. Thereafter, several analysis programs were updated or created (most notably
Curves from Richard Lavery and
NewHelix/FreeHelix from Richard Dickerson), following the loosely defined convention. Even though the parameters are now named the same, the different programs can provide conflicting numerical values, especially for strongly distorted structures. See, for example, Werner et al. (1996) "
Intercalation, DNA kinking, and the control of transcription" [
Science,
271(5250), 778-84].
The 1999 Tsukuba Workshop
Our efforts in "
resolving the discrepancies among nucleic acid conformational analyses" uncovered the source of the disparate descriptions from commonly used software programs:
Growing interest in understanding the relationship between the global folding of nucleic acids and the sequence-dependent structure of individual base-pair steps has stimulated the development of new mathematical methods to define the geometry of the constituent base-pairs. Several approaches, designed to meet guidelines set by the nucleic acid community, permit rigorous comparative analyses of different three-dimensional structures, as well as allow for reconstruction of chain molecules at the base-pair level. The different computer programs, however, yield inconsistent descriptions of chain conformation. Here we report our own implementation of seven algorithms used to determine base-pair and dimer step parameters. Aside from reproducing the results of individual programs, we uncover the reasons why the different algorithms come to conflicting structural interpretations. The choice of mathematics has only a limited effect on the computed parameters, even in highly deformed duplexes. The results are much more sensitive to the choice of reference frame. The disparate schemes yield very similar conformational descriptions if the calculations are based on a common reference frame. The current positioning of reference frames at the inner and outer edges of complementary bases exaggerates the rise at distorted dimer steps, and points to the need for a carefully defined conformational standard.
This work laid the foundation for the standardization of the base-pair parameters in the 1999 Tsukuba Workshop on
Nucleic Acid Structure and Interactions. Following public review and discussion, and final approval by the IUBMB Nomenclature Committee,
the standard base-reference frame paper came out in 2001 [
PDF from the Nucleic Acids Database (NDB)]. From the initiation to its completion, the standardization was made possible by the NDB project, led by Helen Berman.
While not a participant of the 1999 Tsukuba Workshop, I was nevertheless heavily involved in the preparation of the final report. In the following posts at this section, I am planning to provide full data files and scripts so the Figures and Tables can be re-generated. In addition to serving as learning materials for new comers to the field of nucleic acid structures, the details should also be of interest to seasoned practitioners to watch for the caveats. From my own perspective, the work is directly relevant to the automatic identification and classification of non-canonical base pairs in RNA structures, among other possible applications already implemented in or to be added to 3DNA.
To the best of my knowledge, currently only 3DNA and
Curves+ conform to the standard base-reference frame; as a result, the structural parameters (for Watson-Crick base-pair duplexes) calculated by the two programs are very similar.
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Topic: Standards on defining nucleic acid structural parameters (Read 44492 times)