TORSION ANGLE DEPENDENCE OF PHOSPHORUS CHEMICAL SHIFTS IN A NUCLEIC ACID BACKBONE FROM COMBINED MOLECULAR DYNAMICS AND DENSITY FUNCTIONAL CALCULATIONS

J. Přecechtělová^1,2, P. Novák^1,2, M. L. Munzarová^1,2, M. Kaupp³, and V. Sklenář^1,2

¹ National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, CZ-61137 Brno, Czech Republic

² Central European Institute of Technology, Masaryk University, Žerotínovo náměstí 617/9, CZ-60177 Brno, Czech Republic

³ Institut für Chemie, Technische Universität Berlin, Straβe des 17. Juni 135, D-10623 Berlin, Germany

³¹P chemical shifts (δP) in nucleic acids proved to be sensitive to the conformation of the backbone [1]. Therefore, the understanding of torsion angle-chemical shift relationships can aid nucleic acid structure determination. We present a comprehensive study of these relationships relying on density functional (DFT) calculations of δP [2].

The chemical shift calculations were performed using geometries of hydrated dimethyl phosphate (DMP), the model of the phosphodiester linkage, extracted from molecular dynamics (MD) snapshots of [d(CGCGAATTCGCG)]₂. A thorough analysis of δP obtained has shown that while P−O torsion angles α and ζ dominate δP, C−O torsion angles ε and β only modulate the chemical shift trends established by α and ζ. Moreover, the dependences of δP on P−O torsion angles are described by simple functions, which can serve as alternatives to the so-called Karplus equations, typically used in NMR to determine torsion angles. We also present chemical shift maps revealing the joint effects of α and ζ.

A B-DNA backbone undergoes transitions between two conformational states referred to as B_I and B_II. These transitions occurring on a nanosecond time scale influence δP. The chemical shift difference between the pure B_I and B_II states obtained from our calculations is in a very good agreement with the difference inferred from experimental data. The combined MD/DFT approach employed in the study thus proved to bring a considerable improvement over static calculations reported so far.

This work was supported by the Grants MSM0021622413 to M.M. and LC06030 to V.S. from the Ministry of Education, Youth and Sports of the Czech Republic, and by the Grant No. IAA500040903 from the Grant Agency of the Academy of Sciences of the Czech Republic to JP.

1. D. G. Gorenstein, Chem. Rev., 94 (1994) 1315-1338.

2. J. Přecechtělová, P. Novák, M. L. Munzarová, M. Kaupp, V. Sklenář, J. Am. Chem. Soc., 132 (2010) 17139-17148