CONFORMATIONAL CHARACTERISTICS OF DINUCLEOTIDE STEPS VIA SINGLE-CRYSTAL STRUCTURES OF DNA OLIGOMERS. M. A. El Hassan & C. R. Calladine Department of Engineering. University of Cambridge, Cambridge, CB2 1PZ, UK.

In this paper, we investigate the geometry of DNA dinucleotide steps as revealed by single crystal structures of DNA oligomers. We set up a database of 60 naked (= not bound to protein or drug) DNA oligomers, including A-form and B-form oligomers alike. The database contains a total of 400 dinucleotide steps. The geometry of a dinucleotide step is described by the six step parameters (Twist, Roll, Tilt, Rise, Slide and Shift) and the six base-pair parameters (Propeller, Buckle, Opening, Stretch, Shear and Stagger) as given by the Cambridge Accord[1. ] The step and base-pair parameters are extracted from the atomic co-ordinates data of the various oligomers by means of the CEHS scheme that we have recently developed.[2]

In terms of the leading step parameters: Twist, Roll and Slide, we find that some dinucleotide steps are Rigid (= AA/TT, AT, GA/TC), i.e. they adopt more-or-less a single conformation; some are Bistable (= GG/CC, GC, CG) i.e. they adopt one of two distinct conformations; and some are Continuously Flexible (= CA/TG, TA) i.e. they can lie anywhere in a continuous range of conformations. AC/GT shows characteristics intermediate to those of Rigid and Bistable steps, while AG/CT is not included in our classification due to lack of data. We also find that continuously flexible steps exercise their flexibility along a well-defined single-degree-of-freedom path in the Roll/Slide/Twist conformational space^.3

We also present a classification of dinucleotide steps with respect to Propeller. We uncover a striking correlation between the conformational flexibility of a dinucleotide step and the level of Propeller in the constituent base-pairs^.4 We conclude that the level of Propeller in the base-pairs constituting a dinucleotide step results in a stereo-chemical locking effect, the extent of which determines the conformational mobility or otherwise of a dinucleotide step.

1Dickerson, R. E. et al. (1988). EMBO. J. 8: 1-4

²El Hassan, M. A. & Calladine, C.R. (1995). J. Mol. Miol. 251: 648-664

³El Hassan, M. A. & Calladine, C. R. (1996(a)). Conformational Characteristics of DNA; Empirical Classification and a Hypothesis for the conformational Behaviour of Dinucleotide Steps. Phil. Trans. Roy. Soc. (A). Accepted for Publication.

⁴El Hassan, M. A. & Calladine, C. R. (1996(b)). Propeller-Twisting and the flexibility of dinucleotide steps. Submitted for publication.