A purely geometric study aimed at investigating the role of dinucleotide step parameters on curvature and torsion of infinitely repeating DNA sequences is presented. This original approximate formulae of Calladine et al. (1988) are critically examined and a more exact general formula is proposed.
The synthesis of a data--base of sixty naked DNA oligomers: 25 dodecamers, 18 decamers, 16 octamers, 1 tetramer; and 13 DNA/protein co--crystals is described. An extensive empirical study of the geometries of DNA dinucleotide steps in the naked--DNA database is reported and a number of new correlations and classifications that have resulted from this study are described in detail. The main conclusions include the kinematic classification of dinucleotide steps into two main classes: Rigid and Loose (= Flexible or Bistable). ``Continuously--flexible'' steps are shown to exercise their flexibility along a well defined single--degree--of--freedom with Roll, Slide and Twist all approximately linearly correlated. These empirically determined conformational characteristics are then accounted for in terms of: (a)Mechanical stacking effects associated with Propeller--twisting of constituent base--pairs, (b) Chemical stacking effects associated with the special electrostatic charge distributions and (pi) - (pi) effects in homogeneous G|C steps (Hunter, 1993) and (c)Backbone--dictated effects that govern in the absence of (a) and (b). A simple two--parameter model for the conformational description of the backbone is proposed and used to classify the backbone conformations in all entries of our data--base. Some of the mainly backbone--dictated medium--range aspects of the structure of DNA are examined by the application of the techniques of window--averaging and autocorrelation to the leading step parameters and one of the two parameters describing the backbone configuration. The results of these autocorrelation and window averaging analyses are compared closely with the correlations seen in the most flexible steps.
The role of the conformation of DNA in DNA/protein recognition is briefly addressed. This is achieved by carrying out similar studies on protein--bound DNA as those that have been carried out on naked DNA. Despite the scarcity of data on protein--bound DNA, some striking patterns have been uncovered. These include the role of flexible steps in the recognition process as well as the difference in structural behaviour between directly contacted DNA and DNA that bridges two contacted sites in dimeric DNA/protein complexes. The question of whether dinucleotides should be replaced by trinucleotides as fundamental units for the description of the structure of DNA is also addressed by examining, whenever possible, i.e. whenever there are sufficient data, the conformational preferences of flexible steps in all possible trimer contexts.
Key Words: DNA--conformation, dinucleotide step, mid--step--triad,
Euler--angles, repeating DNA sequences, curvature, torsion, oligomers, flexibility,
bistability, rigidity, sugar--phosphate backbone, medium--range conformation
of DNA, protein--bound DNA, near--neighbours.