Stacking interactions in RNA and DNA: Roll‐slide energy hyperspace for ten unique dinucleotide steps

Abstract

Understanding dinucleotide sequence directed structures of nuleic acids and their variability from experimental observation remained ineffective due to unavailability of statistically meaningful data. We have attempted to understand this from energy scan along twist, roll, and slide degrees of freedom which are mostly dependent on dinucleotide sequence using ab initio density functional theory. We have carried out stacking energy analysis in these dinucleotide parameter phase space for all ten unique dinucleotide steps in DNA and RNA using DFT-D by ωB97X-D/6-31G(2d,2p), which appears to satisfactorily explain conformational preferences for AU/AU step in our recent study. We show that values of roll, slide, and twist of most of the dinucleotide sequences in crystal structures fall in the low energy region. The minimum energy regions with large twist values are associated with the roll and slide values of B-DNA, whereas, smaller twist values correspond to higher stability to RNA and A-DNA like conformations. Incorporation of solvent effect by CPCM method could explain the preference shown by some sequences to occur in B-DNA or A-DNA conformations. Conformational preference of BII sub-state in B-DNA is preferentially displayed mainly by pyrimidine-purine steps and partly by purine-purine steps. The purine-pyrimidine steps show largest effect of 5-methyl group of thymine in stacking energy and the introduction of solvent reduces this effect significantly. These predicted structures and variabilities can explain the effect of sequence on DNA and RNA functionality.

Stacking geometry for non‐canonical G:U wobble base pair containing dinucleotide sequences in RNA: dispersion‐corrected DFT‐D study

“…The purine‐purine and purine‐pyrimidine sequences are seen to prefer small roll values while the pyrimidine‐purine sequences have their minimum energy for larger positive roll. Similar base sequence dependent variations in roll in the dinucleotides containing only Watson‐Crick base pairs was seen and characterized earlier . Such variability was explained by Calladine as effect of cross strand purine‐purine steric clash due to negative propeller twist in most of the Watson‐Crick base pairs.…”

“…These indicate very similar trends even by the computationally expensive MP2/6‐31G(2d,2p) method, although the MP2 energies indicate higher stability for the solely G:U base pair containing sequences, namely GU/GU, UG/UG, and GG/UU. Presumably the conserved C3'‐endo sugar pucker of RNA molecules, along with possible hydrogen bonding interactions between 2'‐OH and O4' atoms of ribose sugar of neighboring residues give additional stability to the structures with positive roll values . We observe that GG/CU and GU/AU base pair step conformations are possibly stabilized by additional hydrogen bonds between successive base pairs along or across the strands at high positive roll and negative slide values.…”

“…The optimum value of shear (2.25 Å) was obtained by varying the shear value in generated base pairs by NUCGEN and locating the most favorable hydrogen bonds. We have therefore generated 605 modeled dinucleotide structures for each dinucleotide sequence using above parameters, where the sugar‐phosphate backbone is replaced by methyl group as in normal practice …”

“…Calculation of explicit stacking energy of different non‐canonical base pair containing dinucleotide sequences using ab‐initio quantum chemical methods is computationally challenging. Most of the reported studies on stacking geometry of dinucleotide sequences are done on canonical base pair containing steps of RNA and generally on DNA . We observed recently that along with various ab‐initio methods dispersion corrected density functional theory (DFT‐D) especially ωB97X‐D/631G(2d,2p) is quite satisfactory for estimating stacking energy of different dinucleotide sequences .…”

“…Most of the reported studies on stacking geometry of dinucleotide sequences are done on canonical base pair containing steps of RNA and generally on DNA . We observed recently that along with various ab‐initio methods dispersion corrected density functional theory (DFT‐D) especially ωB97X‐D/631G(2d,2p) is quite satisfactory for estimating stacking energy of different dinucleotide sequences . Extending our previous understanding on generation of stacking energy landscapes in dinucleotide parameter hyperspace, in this work, we have focused on the dinucleotide sequences formed by the canonical W:WC base pairs (A:U or G:C) and non‐canonical G:U W:WC base pair.…”