Nucleic acid structure analysis: A users guide to a collection of new analysis programs

Common nomenclature describing the geometry of nucleic acid structures was established at a 1988 EMBO Workshop on DNA Curvature and Bending (Diekmann, S. (1988)7 Mol. Biol. 208, 787-791; Diekmann, S. (1989) The EMBO Journal 8, 1-4; Sarma, R.H. (1988)7 Biomol. Structure & Dynamics 6, 391-395; Dickerson, R.E. (1989)J Biomol. Structured Dynamics 6, 627-634; Dickerson, RE. et al. (1989)Nuc. Acids Res. 17, 1979-1803). We have subsequently developed and incorporated sophisticated mathematics in a computer program to calculate the parameters described by the guidelines. The program calculates all the local parameters relating complementary bases and neighboring base and base pairs in both Cartesian and helical coordinate frames. In addition, the main mathematical property requested by the EMBO guidelines—that the magnitude of the parameters be independent of strand or direction of measurement—is accomplished without the use of a midway coordinate frame for the rotational parameters. The mathematics preserve the physical intuition used in defining the parameters; in particular, the rotational parameters are true rotations based on a simple physical model (rotation at constant angular velocity for a unit amount of time), not Euler angles or angles between vectors and planes as is the case with other approaches. As a result, the mathematical equations are symmetric with the property that a 5° tilt is the same as a 5° roll or a 5° twist, except that the rotations take place about different axes. In other approaches, a 5° tilt can mean a different amount of net rotation from a 5° roll or a 5° twist. In addition, a great deal of flexibility is built into the pro-gram so that the user has control over the analysis, including the input format, the coordinate frame used for the base pairing relationship, the point about which the rotations are performed, and which geometric relationships are analyzed. While there is a great deal of flexibility, the program is easy to use. Interactive queries and user accessible files make the options in the program very convenient to tailor to individual needs. In addition, there is also a program that calculates bond lengths, valence angles, and torsion angles along the nucleic acid backbone, and within the sugar and base rings. Another program ’learns’ the identities of the bond lengths, valence angles, and torsion angles that the user would like to determine. This last program is especially useful for calculating the hydrogen bonds between atoms in complementary strands as well as the unusual hydrogen bonds found in recently determined nucleic acid NMR structures or within protein/nucleic acid complexes.