Structural Variability and the Nature of Intermolecular Interactions in Watson−Crick B-DNA Base Pairs

Abstract

A set of nearly 100 crystallographic structures was analyzed using ab initio methods in order to verify the effect of the conformational variability of Watson-Crick guanine-cytosine and adenine-thymine base pairs on the intermolecular interaction energy and its components. Furthermore, for the representative structures, a potential energy scan of the structural parameters describing mutual orientation of the base pairs was carried out. The results were obtained using the hybrid variational-perturbational interaction energy decomposition scheme. The electron correlation effects were estimated by means of the second-order Møller-Plesset perturbation theory and coupled clusters with singles and doubles method adopting AUG-cc-pVDZ basis set. Moreover, the characteristics of hydrogen bonds in complexes, mimicking those appearing in B-DNA, were evaluated using topological analysis of the electron density. Although the first-order electrostatic energy is usually the largest stabilizing component, it is canceled out by the associated exchange repulsion in majority of the studied crystallographic structures. Therefore, the analyzed complexes of the nucleic acid bases appeared to be stabilized mainly by the delocalization component of the intermolecular interaction energy which, in terms of symmetry adapted perturbation theory, encompasses the second- and higher-order induction and exchange-induction terms. Furthermore, it was found that the dispersion contribution, albeit much smaller in terms of magnitude, is also a vital stabilizing factor. It was also revealed that the intermolecular interaction energy and its components are strongly influenced by four (out of six) structural parameters describing mutual orientation of bases in Watson-Crick pairs, namely shear, stagger, stretch, and opening. Finally, as a part of a model study, much of the effort was devoted to an extensive testing of the UBDB databank. It was shown that the databank quite successfully reproduces the electrostatic energy determined with the aid of ab initio methods.

Challenging Dogmas: Hydrogen Bond Revisited

“…99 ). This conclusion is in accord with a recent study by Czyznikowska et al, 100 where the hybrid variational-perturbational interaction energy decomposition scheme was used. We thus strongly suggest that the widely used classication of intermolecular interactions (H-bonded/dispersion-dominated/mixed) 101 would be better and more physically sound to change to a new one (induction-dominated/dispersion-dominated/mixed).…”

Transferable aspherical atom model refinement of protein and DNA structures against ultra-high-resolution X-ray data

“…, which are in agreement with previous theoretical studies (Czyżnikowska et al, 2010), and is additionally stabilized by stacking contacts with alternate average energy levels of À2 and À15 kcal mol Residual density around Ile16, Tyr29, His40, His57, His91 and Ser139 in the trypsin structure after IAM (left) and TAAM (right) refinement, with polar H atoms of the residues omitted. The blue isosurface is drawn at +0.13 e Å À3 and the red isosurface is drawn at À0.13 e Å À3 .…”

Vibrational solvatochromism. II. A first-principle theory of solvation-induced vibrational frequency shift based on effective fragment potential method

“…Note that, in the cases of typical H-bonded complexes, while the charge-transfer energy is usually a minor component in the total binding energy, 53 the contributions from exchangerepulsion, charge-delocalization, and dispersion are known to be large. [54][55][56] Therefore, the detailed physical origins of vibrational solvatochromism beyond the first-order electrostatic approximation remain still unknown.…”