B-DNA structure is intrinsically polymorphic: even at the level of base pair positions

Abstract

Increasingly exact measurement of single crystal X-ray diffraction data offers detailed characterization of DNA conformation, hydration and electrostatics. However, instead of providing a more clear and unambiguous image of DNA, highly accurate diffraction data reveal polymorphism of the DNA atomic positions and conformation and hydration. Here we describe an accurate X-ray structure of B-DNA, painstakingly fit to a multistate model that contains multiple competing positions of most of the backbone and of entire base pairs. Two of ten base-pairs of CCAGGCCTGG are in multiple states distinguished primarily by differences in slide. Similarly, all the surrounding ions are seen to fractionally occupy discrete competing and overlapping sites. And finally, the vast majority of water molecules show strong evidence of multiple competing sites. Conventional resolution appears to give a false sense of homogeneity in conformation and interactions of DNA. In addition, conventional resolution yields an average structure that is not accurate, in that it is different from any of the multiple discrete structures observed at high resolution. Because base pair positional heterogeneity has not always been incorporated into model-building, even some high and ultrahigh-resolution structures of DNA do not indicate the full extent of conformational polymorphism.

The Effect of DNA Sequence Directionality on G‐Quadruplex Folding

“…It has been shown, however, that double-and triplestranded DNAs exhibit conformational polymorphism of the backbone and base pairs that in turn lead to different stacking interactions and thermal stability of the DNAstructure(s). [5][6][7][8] Predicted helical parameters exhibit different values for pairs of oligonucleotides with reversed sequence ( Figure S1 in the Supporting Information). If sequence inversion influences the structure of more common double-stranded DNA( e.g., different behavior of AT and TA base-pairs), [9][10][11] then its effect on more complex G-quadruplexes would be expected to be substantial.…”

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC)

“…Through the published structures of small to moderately sized DNA duplexes in the PDB [4] and Nucleic Acid Database [5,6], we have a fair-to-excellent understanding of the variations in sequence dependent DNA structure at the di- to tetra- nucleotide level. Although most structures in the databases tend to hide dynamics due to ensemble and time averaging, some extremely high resolution DNA crystal structures [7] have been able to trap multiple DNA backbone conformational substates. Relaxation dispersion NMR experiments have been able to identify transient and low populated Hoogsteen base pairs [8] in DNA duplexes, and solid state NMR experiments have been able to identify large amplitude dynamics in the sugar puckers at CpG steps in crystals [9] of the Dickerson dodecamer.…”

DNA A-tracts Are Not Curved in Solutions Containing High Concentrations of Monovalent Cations

“…18–21 The curvature is delocalized; some bending of the helix backbone occurs within the A-tract, while other bends occur at ApT and TpA base pair steps and/or at junctions between the A-tracts and their flanking sequences. 19–21 DNA A-tracts usually have narrow minor grooves, propeller-twisted A·T base pairs and bifurcated hydrogen bonds across the major groove 18, 22–27 (but see Ref. 28).…”