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RESEARCH PRODUCT

B-DNA Structure and Stability as Function of Nucleic Acid Composition. Dispersion-Corrected DFT Study of Dinucleoside-Monophosphate Single and Double Strands

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actions of the sugar-phosphate skeleton with water; (6) hydrophobic interactions of the DNA cylindrical core, made up by the hydrogen-bonded and stacked nitrogen bases, with the water solvent. Recently, there has been increasing effort in developing and applying quantum chemical methods able to reproduce the structure of native B-DNA and to correctly describe the energy involved in the intrastrand and interstrand noncovalent interactions between the nucleotide monomers. This topic has been approached by both wave function methods and density functional theory. [2] Water solvent and sodium counterions also play an important role in the formation and relative stabilization of the double-helical DNA structure because they mitigate the aforementioned long-range electrostatic repulsions among the phosphate groups in the DNA backbone and amplify p–p stacking interactions through the hydrophobic effect. This issue has been recently considered in the choice of model systems in density functional theory (DFT) calculations of the structure of dinucleoside monophosphate single strands. [3] The results obtained show that, not unexpectedly, the presence of the Na + counterions at each phosphate group is even more important than the presence of the implicit solvent for providing a structure in which the relative base–base orientation and the backbone torsion angles are in better agreement with experimental B-DNA crystal structures. This result reconfirms the importance of charge neutralization in DNA model systems. A complicating aspect of DNA in computational studies is the combination of the large size of model systems in combination with the high demand on accuracy for describing the We have computationally investigated the structure and stability of all 16 combinations of two out of the four natural DNA bases A, T, G and C in a di-2’-deoxyribonucleoside-monophosphate model DNA strand as well as in 10 double-strand model complexes thereof, using dispersion-corrected density functional theory (DFT-D). Optimized geometries with B-DNA conformation were obtained through the inclusion of implicit water solvent and, in the DNA models, of sodium counterions, to neutralize the negative charge of the phosphate groups. The results obtained allowed us to compare the relative stability of isomeric single and double strands. Moreover, the energy of the Watson–Crick pairing of complementary single strands to form double-helical structures was calculated. The latter furnished the following increasing stability trend of the doublehelix formation energy: d(TpA)2 < d(CpA)2 < d(ApT)2 < d(ApA)2 < d(GpT)2 < d(GpA)2 < d(ApG)2 < d(CpG)2 < d(GpG)2 < d(GpC)2, where the energy differences between the last four dimers, d(ApG)2, d(CpG)2, d(GpG)2 and d(GpC)2, is within 4.0 kcal mol � 1 , and the energy between the most and the least stable isomers is 13.4 kcal mol � 1 . This trend shows that the formation energy essentially increases with the number of hydrogen bonds per base pair, that is two between A and T and three between G and C. Superimposed on this main trend are more subtle effects that depend on the order in which bases occur within a strand from the 5’- to the 3’-end.