Definitions and nomenclature of nucleic acid structure parameters.

At an EMBO Workshop on DNA Curvature and Bending, held at Churchill College, Cambridge, on 10-15 September 1988, two sessions were scheduled on definitions of parameters used to describe the geometry of nucleic acid chains and helices, and a common nomenclature for these parameters. The most widely used library of helix analysis programs, HELIB (Fratini et al., 1982; Dickerson, 1985) suffers from the fact that the translations and rotations as defined are not fully independent and depend to a certain extent upon the choice of overall helix axis. Several research groups have been engaged independently in developing alternative programs for the geometrical analysis of polynucleotide chains, but with different definitions of quantities calculated and with widely different nomenclature even when the same parameter was involved. The EMBO work sessions involved four such programming groups and other potential users, and had as its goal the introduction of a common set of concepts and common language for greater ease of communication. It is hoped that the standards agreed upon and reported in this note will prove acceptable to others in the field, and ultimately will be approved by the IUPAC/IUB Commission on Biochemical Nomenclature (IUPAC/IUB Joint Commission on Biological Nomenclature, 1983). The following points were agreed upon at the EMBO Workshop: (i)The stated goal in program development is the creation of a new and optimized library of routines for the analysis and description of polynucleotide structure, especially but not exclusively the DNA double helix. This general purpose library is intended mainly for those who solve nucleic acid structures using X-rays, NMR or other physical techniques and those who are interested in these results. It is recognized that theoretical studies will require more elaborate and more specialized programs, but it is felt that the first order of business is the creation of a simple, easily used library calculating easily understood and physically meaningful structure parameters. In particular, the-new analysis routines should involve the least possible change from the familiar HELIB library that has been in use for more than five years, consonant with making the three rotations and three translations leading from one base pair to the next mathematically independent. (ii) Trial programs developed by several research groups are to be circulated to interested users over the next 12 18 months for practical evaluation, before any attempt is made to select a 'standard' library. Programs will be contributed by the following four groups, but others may participate if desired: a. Richard Lavery and Heinz Sklenar (Lavery and Sklenar, 1988) b. D.M. Soumpasis and Chang-Shung Tung (Soumpasis and Tung, 1988) c. E.von Kitzing and S.Diekmann (von Kitzing and Diekmann, 1987) d. Manju Bansal (Bhattacharya and Bansal, 1988) Each of the programming participants will apply the resulting routines to three test cases: the Drew Native B-DNA of sequence C-G-C-G-A-A-T-T-C-G-C-G, an A-DNA structure to be supplied by Andrew H. -J.Wang and a tRNA molecule. The tables of parameters generated will be circulated to all interested parties for comparison. (iii) All programs should have as a user option the choice of base pairs versus individual bases of a single strand. They should also allow calculations to be carried out relative to local helix axes (from one base pair to the next), and relative to a long-range or global axis. (iv) The x direction of a local or base pair coordinate set should point along the short axis of the base pair, the y direction along the long axis and the z direction perpendicular to the plane of the pair, in a right-handed orthogonal axial set. (Directions of positive x, y and z are considered below, following defintions of parameters.) The long axis of a base pair can be defined either by the line from the C6 of a pyrimidine to the C8 of a purine, or alternatively by the line from C6 to a hypothetical C8* atom on the purine, chosen so that the C6-C8* vector is parallel to the Cl'-Cl' vector. (The choice used should be stated explicitly.) If desired, employment of axes along the three principal moments of inertia of a base pair may be incorporated as an extra user option, but should not replace the simpler defintions. (v) Axes for calculating parameters of each base pair step should be chosen so that the same numerical values result (with only a possible change of sign) when going from base pair 1 to base pair 2, as from base pair 2 to 1. One way in which this can be accomplished is by choosing a local reference axis set intermediate between those of the base pairs themselves. (vi) The agreed-upon common nomenclature of parameters is as follows, using Greek letters for rotations and Roman letters for translations in accordance with IUPAC recommended practice.