MD/DFT STUDY OF ENVIRONMENTAL EFFECTS ON 31P CHEMICAL SHIFT TENSORS IN B-DNA
J. Přecechtělová1, P. Novák1, M. Kaupp2, M. L. Munzarová1 and V. Sklenář1
1 National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, CZ-611 37 Brno, Czech Republic
2 Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074, Germany
31P NMR techniques have become a powerful tool to probe the conformation of the phosphodiester backbone in nucleic acids . A few years ago, a new method based on 31P chemical shift anisotropy (CSA) was suggested for constraining the orientation of the phosphate groups relative to the molecular alignment tensor . This method, though very helpful in nucleic acid (NA) structure determination, suffers from adopting an assumption that the 31P CSA tensor is uniform for all backbone phosphates in oligonucleotides. In order to check the justification of such an assumption, we have attempted to perform a combined MD/DFT study of 31P chemical shift (CS) tensors.
For this purpose we tested three models differing in the size of the sugar-phosphate backbone involved. As the study requires a very precise description of environmental effects, we have also carried out a series of validation calculations to find the optimal strategy for the solvent treatment and the treatment of long-range polarization effects. The tested methodologies included an explicit solvent, the PCM-COSMO model and the charge-field perturbation approach that was used to model water molecules lying beyond the first solvation shell by explicit partial point charges. To reduce the computational costs we took the following steps: 1. the geometries were taken from the molecular dynamics simulation without reoptimizing, 2. the resolution-of-identity (RI) approximation as implemented in Turbomole5.6 was employed for the wavefunction calculations, and 3. locally dense basis sets were used in NMR calculations performed at the DFT level.
The calculated 31P chemical shift tensors show a strong sensitivity to the method of the solvent treatment – the combinations of the explicit solvent with the PCM-COSMO model and the point charges, respectively, give qualitatively different chemical shift tensors. In addition, the comparison of the chemical shift tensors for the three models reveal nonintuitive trends. These results will serve as a basis for the careful choice of the appropriate methodology to calculate an average of the 31P chemical shift tensors over the molecular dynamics trajectory of the oligonucleotide d(CGCGAATTCGCG)2.
Acknowledgment: This work was supported by the grant MSM0021622413 from the Ministry of Education, Youth and Sports of the Czech Republic.
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