STATISTICAL-ANALYSIS OF DNA DUPLEX STRUCTURES IN SOLUTION DERIVED BY HIGH-RESOLUTION NMR

An initial statistical analysis has been performed on the helical para meters for the solution structures of three DNA duplexes recently solv ed in this laboratory by proton NMR. Local conformations in these stru ctures belong to the B family of forms; nevertheless they display a st rong sequence-dependent heterogeneity akin to that found in single cry stals and by theoretical calculations. However, average helical parame ters as well as their variations are quite different for short DNA fra gments in solution and in crystal. Average helical twist in three NMR- refined oligonucleotides is 34.6-degrees, in remarkable agreement with independent solution-state data, while helical twist is 36-degrees fo r DNA in crystals. Other characteristic features of solution DNA confo rmations are negative slide, systematically open minor groove (for alm ost all sequences), and decreased helical rise. The latter, rather une xpected finding, is correlated with a surprisingly strong non-flatness of Watson-Crick base pairs. Deviations of base pairs from planarity p roved to be a significant source of conformational variability; of par ticular importance is base stagger, which is often missed in structura l analysis of DNA. Several new structural parameters have been introdu ced for dinucleotide steps, characterizing non-planar geometries of co nstituent base pairs; these parameters show a significant degree of co rrelation with traditional step parameters (twist, tilt, roll, shift, slide, rise). Many sequence-dependent features are observed in solutio n structures; variation of roll and slide parameters occurs according to ''Calladine's rules'', while variation of helical twist appears to oppose them. However, a larger set of solution structures is needed to complete the analysis of sequence dependence of DNA conformation.