Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands

Abstract

Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment. For both DNA and RNA, SSD conformations are observed that are either close to the A-form, or close to the B-form, or intermediate between the two forms, or further away from either form, illustrating the local structural heterogeneity near the stacked state. Among this large variety of distinct conformations, several common stacking patterns are observed between DNA and RNA, and between nucleic acids in isolation or in complex with proteins, suggesting that these might be stable stacking orientations. Noncanonical face/face orientations of the two bases are also observed for neighboring bases in the same strand, but their frequency is much lower, with multiple SSD sequences across categories showing no occurrences of such unusual stacked conformations. The resulting reduced set of stacking geometries is directly useful for stacking-energy comparisons between empirical force fields, prediction of plausible localized variations in single-strand structures near their canonical states, and identification of analogous stacking patterns in newly solved nucleic acid containing structures.

Protonation of Guanine:5‐Methylcytosine and Guanine:Cytosine Base Pairs in Duplex Oligodeoxyribonucleotides

“…Analogous nearest-neighbour effects have been reported for very short oligoribonucleotides, e. g. GAA [40][41][42] and for a single-stranded hexadeoxyribonucleotide, d-AGGCCT, [6] where the hydrogen resonances on adenine and cytosine bases were shifted in response to the deprotonation (at pH around 10) of neighbouring thymine or guanine groups. Such results reflect the importance of stacking interactions between the bases [43,44] even in single-stranded nucleic acids.…”

SN- and NS-puckered sugar conformers are precursors of the (6–4) photoproduct in thymine dinucleotide

“…Interestingly, various thymine dinucleotide stacking geometries have been identified in single-stranded regions of nucleic acid crystal structures. 34,35 Our results are likely to be useful to identify staked state candidates as proreactive species based on their sugar pucker combination.…”

The extent of B-form structure in a 6S RNA variant that mimics DNA to bind to the Escherichia coli RNA Polymerase

“…We showed that RNA SSDs approach a B-form structure in many instances, 3 and this local B-form structure seems to be achieved through both C2 -endo sugar conformations or base stacking patterns that resemble B-form DNA stacking. 4 Interestingly, the base RMSD values show a greater propensity for B-form structures than the sugar-phosphate backbone at the SSD level, which suggests an under-representation of B-form-like sugar-phosphate conformations for RNA in the PDB models. While duplex RNA usually adopts an A-form structure with its furanose sugars assuming C3 -endo pucker conformations, 5 the C2 -endo pucker is present in some functional RNA motifs, and may possibly be implicated in RNA folding.…”