CONFORMATIONAL CHARACTERISTICS OF DNA - EMPIRICAL CLASSIFICATIONS ANDA HYPOTHESIS FOR THE CONFORMATIONAL BEHAVIOR OF DINUCLEOTIDE STEPS

This paper is concerned with an investigation of the geometry and stru cture of DNA as revealed by X-ray diffraction of single crystal oligom eric structures. A database of atomic coordinates of 60 naked (i.e. no t bound to any protein or drug) DNA oligomers (25 dodecamers, 18 decam ers, 16 octamers and 1 tetramer) is set up and carefully described. An extensive empirical study of the geometries of DNA dinucleotide steps in the database, involving only unmodified Watson-Crick base pairs (A -T and G-C), is reported, and a number of new correlations and classif ications are described in detail. The main conclusions include the kin ematic classification of dinucleotide steps into two main classes: rig id and loose (or flexible or bistable). 'Continuously flexible' steps are shown to exercise their flexibility along a well-defined single-de gree-of-freedom pattern, with roll, slide and twist all correlated lin early. The rigid steps are AA/TT, AT and GA/TC, and the loose (bistabl e) steps are GG/CC, GC, CG while the loose (continuously flexible) ste ps are CA/TG and TA. AC/GT is the least clear of all steps and it is p erhaps best described as neither a rigid nor a loose step but rather a n 'intermediate' step. The base-pair parameters are also carefully exa mined and the resulting pivotal correlation between the average propel ler and the flexibility of the step (equals the standard deviation of slide), that we have recently described elsewhere (El Hassan & Calladi ne 1996), is examined in some detail. A simple two-parameter scheme fo r the description of the conformation of the sugar phosphate backbone is given and used to classify the sugar phosphate backbones in all ent ries of our database into A-backbone and B-backbone conformations. The role of the backbone in determining the conformational preferences of the dinucleotide steps is examined by demonstrating that whereas the B-backbone conformation permits a fairly narrow channel in the roll/sl ide/twist conformational space, with all three parameters linearly cor related, the A-backbone allows only a small 'box' region near the high -roll, low-twist, low-slide end of the space. Finally, the empirically determined conformational characteristics of the various dinucleotide steps are accounted for in terms of (a) mechanical stacking effects a ssociated with propeller-twisting of constituent base pairs (the prope ller-flexibility correlation), (b) chemical stacking effects associate d with the special electrostatic charge distributions and pi-pi effect s in homogeneous G/C steps (Hunter 1993), and (c) backbone-dictated ef fects that govern in the absence of (a) and (b).