Ab Initio Calculations of NMR Parameters in Nucleic Acids
Quantum chemical calculations of nuclear magnetic shielding tensors and indirect nuclear spin-spin coupling constants are becoming increasingly important in reproducing, predicting and interpreting experimental NMR data in biomolecules. Our research interests focus on computing and understanding NMR parameters of building blocks of nucleic acids (bases and base pairs, genuine and modified nucleosides, sugar-phosphate backbone models) by means of ab inito quantum mechanics. The method most often applied is the Density Functional Theory (DFT). Isotropic chemical shielding and spin-spin coupling constants in nucleosides have been in our group theoretically studied for a series of anhydrodeoxythymidines . Further studies of the chemical shielding have been performed for a series of genuine deoxyribonucleosides (deoxyadenosine, deoxyguanosine, deoxycytidine, deoxythymidine). In particular, the effect of the glycosidic torsion angle χ and the sugar pucker on the chemical shifts has been explored.
The chemical shielding is a tensor property and the knowledge of the principal components and their orientation is often important. The ab initio prediction of 1H and 13C chemical shielding tensors in adenide, guanine, uracile, cytosine and thymine bases have been used to assist the development of TROSY NMR experiments for intra-residual correlations between base and sugar protons in isotope-labeled DNA and RNA oligonucleotides.
In 2000 we performed also the first systematic calculations of 1H and 15N chemical shielding tensors in nucleic acid base pairs as a function of hydrogen bond length. Further study of the influence of base pairing on the chemical shielding tensors of bases is in progress for the case of the [d(G4T4G4)]2 quadruplex. Apart from reproducing the available experimental data, we aim at an understanding of the different sensitivity of NMR parameters of various atoms to the base pairing. In the future, we wish to study the effects of the base stacking and of the solvent on the NMR parameters, as well as to understand various aspects of the base pair stability.
An extensive study has been devoted to spin-spin coupling in genuine and modified nucleosides as a function of the glycosidic torsion. The study has revealed a striking dependence of the Karplus relationships between the three-bond coupling across the glycosidic bond and the glycosidic torsion on the base.
In another study, we have performed quantum chemical calculations to investigate the relation between scalar couplings and conformations around the glycosidic bond also in 19F labeled pyrimidine oligonucleotides. It has been found that the theoretical dependence of the unusual couplings, observed across 5 bonds - 5J(H1Ž, F), on the torsion angle χ can be described by a generalized Karplus relationship. The analysis based on density functional theory has been employed.
In our recent paper, density functional theory (DFT) has been applied to study the conformational dependence of 31P chemical shift tensors in B-DNA. The gg- and gt-conformations of backbone phosphate groups representing BI and BII-DNA have been explored. Calculations were preformed on static models of dimethylphosphate (dmp) and dinucleoside-3?,5?-monophosphate with bases replaced by hydrogen atoms (sPs) in vacuo as well as in an explicit solvent. Trends in 31P CSA chemical shift tensors with respect to the backbone torsion angles α, β, ε, and ζ have been presented.