Energy hyperspace for stacking interaction in AU/AU dinucleotide step: Dispersion‐corrected density functional theory study

Abstract

Double helical structures of DNA and RNA are mostly determined by base pair stacking interactions, which give them the base sequence-directed features, such as small roll values for the purine-pyrimidine steps. Earlier attempts to characterize stacking interactions were mostly restricted to calculations on fiber diffraction geometries or optimized structure using ab initio calculations lacking variation in geometry to comment on rather unusual large roll values observed in AU/AU base pair step in crystal structures of RNA double helices. We have generated stacking energy hyperspace by modeling geometries with variations along the important degrees of freedom, roll, and slide, which were chosen via statistical analysis as maximally sequence dependent. Corresponding energy contours were constructed by several quantum chemical methods including dispersion corrections. This analysis established the most suitable methods for stacked base pair systems despite the limitation imparted by number of atom in a base pair step to employ very high level of theory. All the methods predict negative roll value and near-zero slide to be most favorable for the purine-pyrimidine steps, in agreement with Calladine's steric clash based rule. Successive base pairs in RNA are always linked by sugar-phosphate backbone with C3'-endo sugars and this demands C1'-C1' distance of about 5.4 Å along the chains. Consideration of an energy penalty term for deviation of C1'-C1' distance from the mean value, to the recent DFT-D functionals, specifically ωB97X-D appears to predict reliable energy contour for AU/AU step. Such distance-based penalty improves energy contours for the other purine-pyrimidine sequences also. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 107-120, 2014.

Contribution of phenylalanine side chain intercalation to the TATA-box binding protein–DNA interaction: molecular dynamics and dispersion-corrected density functional theory studies

“…It was shown recently that results with dinucleotides including the sugar-phosphate backbone are very similar to those obtained by considering bases only [46]. Use of methyl groups mimicking sugars was also seen to give excellent results [35,40,47]. Both classical and DFT-D calculations indicate that the interaction between the intercalator and DNA bases is quite strongly attractive and that it has a specific role in stabilizing the kinks formed in the DNA structure.…”

“…Instead of the sugar-phosphate backbone we attached a methyl group with the bases as previously done in other studies (Fig. 2) [35,60]. An ethyl group is added with the phenyl ring instead of s protein chain, which can be considered as ethylbenzene (Fig.…”

“…Several dispersion-corrected DFT (DFT-D) methods have been tested by various groups for estimation of stacking interaction [1,[29][30][31][32][33][34]. By comparing several such DFT-D methods, we recently found that ωB97X-D/6-31G(2d,2p) is most suitable for nucleic acid systems [35]. Here, we also explored the energetic basis of the stability of the intercalated Phe residues to maintain the kinks at the two ends of the TATA box.…”

“…Both classical and DFT-D calculations were performed to study the energetics of interaction between the base pair steps of DNA and the hydrophobic phenylalanine side chain. It was reported that the DFT-D method yields results with a chemical precision (<1 kcal mol −1 ) that is comparable to highly accurate CCSD/(T)/complete basis set limit calculations, and is capable of describing the hydrogen bonding and dispersion interactions known to make an important contribution to base pair stacking and ligand-nucleobase interactions [1,[35][36][37][38][39][40][41][42][43][44][45]. We carried out geometry optimizations of two base paired dinucleotide steps, considering the base atoms by replacing the sugar-phosphate backbone atoms with methyl group along with the intercalated Phe residue, replacing the protein main chain with an ethyl group, using the ωB97X-D/6- Fig.…”

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

“…It is now well established that among the dinucleotide step parameters, roll, slide, and twist show significant sequence dependent variation . A thorough scan along these degrees of freedom is thus expected to give good indication about preferred structures and structural variations of different dinucleotide steps.…”