DFT Study of B-like Conformations of Deoxydinucleoside Monophosphates Containing Gua and/or Cyt and their Complexes with Na⁺Cation

Abstract

B-like minimum energy conformations of deoxydinucleoside monophosphate anions (dDMPs) containing Gua and/or Cyt and their Na+ complexes have been studied by the DFT PW91PW91/DZVP method. The optimized geometry of the dDMPs is in close agreement with experimental observations and the obtained minimum energy conformations are consistent with purine-purine, purine-pyrimidine, and pyrimidine-purine arrangements in crystals of B-DNA duplexes. All the studied systems are characterized by pyramidalization of the amino groups, which participate in the formation of unusual hydrogen bond between the carbonyl oxygen of the second base in the dGpdC, dCpdG dDMPs, and their Na+ complexes. In all the obtained structures the bases assume a nearly parallel disposition to each other and this effect is independent on the degree of their spatial superposition. From this it is concluded that the parallel disposition of the bases in the B-like single-stranded conformations is dictated by the sugar-phosphate backbone. Correspondingly, the base-base interactions attain a secondary role in the formation of these spatial structures. The formation of a weak C6-H6...O5' hydrogen bond between cytosine and the phosphate oxygen is reported, in agreement with experimental observations.

DFT study of polymorphism of the DNA double helix at the level of dinucleoside monophosphates

“…The conformational characteristics of the optimized structures having various base sequences will be compared with the corresponding characteristics of the BI-like dDMP structures obtained earlier [3,4]. In common, the three groups of the obtained structures (A, BI, and BII) correspond to anti parallel right-handed DNA duplexes with an anti conformation of the nucleosides.…”

“…The mutual base arrangement in dDMP is sequence dependent, namely two dDMPs with the same nucleoside content but different base sequence (e.g., dApdC and dCpdA) have drastically differed mutual base positions. These observations lead us to the conclusion of principal contribution of the sugar-phosphate backbone to the three-dimensional structure of the DNA single strand, and a minor contribution to these effects can be attributed to base-base stacking interactions [3,4]. Surely, dispersive base-base interactions contribute substantially to the DNA duplex stability and deformability, but they cannot explain the nearly parallel arrangements of the bases with nearly negligible overlap or the essential difference between purine-pyrimidine and pyrimidine-purine base arrangements.…”

“…In the light of these difficulties, our previous studies [3,4] were necessarily limited to consideration of the B-family-like structures of deoxydinucleoside monophosphates, while focusing the attention on elucidating the dependence of the three-dimensional structure of the dDMPs on their nucleotide sequence. Our DFT computations revealed that the characteristic BI-type conformation of DNA duplexes is initially predisposed in the single strand and namely in its dDMP conformational profile in the form of a local energy minimum.…”

“…To evaluate the contribution of the intra-strand conformational preferences to the variation of the DNA duplex structure, we recently performed first-principles quantum mechanical (QM) calculations of minimal fragments of DNA chains using density functional theory (DFT) methods [3,4]. This level of theory provides a reasonable compromise between accuracy and resource demand among the available non-empirical computational methods.…”

Hetero-association of aromatic molecules in aqueous solution

“…Derivatives of nucleic acid bases tend to form stacking-type complexes in aqueous solutions with minor contribution, if any, from in-plane hydrogen-bonding (base-pairing), as deduced from the monotonic shift of aromatic protons to lower frequency in NMR [70,83,85,86,88,89] or the hypochromic effect in UV-vis spectroscopy [90][91][92] on increasing concentration or decreasing 16 M.P. Evstigneev temperature, and also supported by high-level quantum-chemical computations [93][94][95][96]. Lowering the pH of the medium leads to protonation of purine and pyrimidine rings, which is considered to result in weakening of their stacking ability with other molecules [70,97].…”