DNA conformations and their sequence preferences

Abstract

The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with α/γ switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.

The Role of Unconventional Hydrogen Bonds in Determining BII Propensities in B-DNA

“…The reader should be aware that when comparing NMR, MD simulations, and X-ray structures, differences exist between the specific BII percentages assigned to some base pairs steps 12,21 . The sources of uncertainties from crystal structures have being discussed several times and are clearly related to low resolution (frequently insufficient to define backbone's states), lack of dynamics, and lattice restraints 13,25,26 . In the same way, changes in NMR's refinement protocols or annealing procedures from one experiment to another 27,28 , the usually low number of restraints due to the low density of protons in DNA, and the frequent overlap of several NOE peaks 20 , are the main sources of uncertainties, being the average standard deviation in the prediction of BII percentages ±8 21 .…”

“…The canonical state, referred to as BI, features ε/ζ in a trans/gauche-(t/g-) conformation, while the other state, BII, has ε/ζ in g-/t conformation. To determine BI/BII equilibrium in B-DNA, proton and Phosphate NMR experiments [4][5][6][7] , Molecular Dynamics (MD) simulations [8][9][10] , and data mining of crystal structures from databases [11][12][13] have being historically used as the preferred methods. Following initial observations based on crystal structures showing that BI/BII transitions were associated with base destacking and minor groove widening 14,15 , computer MD simulations have shed light on the influence of water and ion dynamics on the propensity of BI/BII states 8,9,16,17 .…”

“…Also based on crystal structures, successive nucleotide in one strand have been shown to have anti-correlated backbone conformational states 11,13 . From the very beginning, 31 P-NMR distinct tetranucleotides 9,10 .…”

Computational Methods for RNA Structure Validation and Improvement

“…A DNA side note: DNA structure can be validated by traditional model-todata match and covalent geometry, and by all-atom contacts, but the RNA conformational tools are unfortunately not valid for DNA because it is more locally flexible, with broader torsion-angle preferences and more sugar-pucker states accessible (Svozil, Kalina, Omelka, & Schneider, 2008).…”

Targeting G-Quadruplex DNA with Small Molecules

“…[3] Since then, the B-form double helix has usually been regarded as the biologically relevant structure of DNA, however in the context of nucleosome core particles and other nucleoprotein complexes DNA can adopt a wide variety of conformations including highly distorted A-, B-, Zform double helices. [4] By necessity, DNA structures are highly dynamic and their associated functions are potentially diverse. In addition to various duplex structures, single-stranded DNAs can fold into a wide variety of hairpin, triplex, G-quadruplex, and i-motif structures containing non-canonical base pairs.…”