NMR DISTANCE RESTRAINTS AT LOW TEMPERATURES -- AN APPLICATION TO A DNA HAIRPIN

 

Michaela Matejková, Radovan Fiala, Petr Padrta and Vladimír Sklenář

 

National Center for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, CZ-611 37 Brno, Czech Republic

 

       Short DNA hairpins play a significant role in a number of biological processes. The most

interesting feature of the oligonucleotides with a general sequence d(GCGNAGC) (N = A, G, C, T) is their extraordinary stability represented by high melting temperatures, polyacrylamide gel mobility and resistance against nucleases. Detailed knowledge of these structures helps understand their unique behavior.

       The d(GCGAAGC) structure has been solved previously by NMR spectroscopy using the NOE-derived distances, torsion angles and residual dipolar couplings [1]. The aim of the present study is a new structure calculation based on NOE data measured at temperatures below 273 K when the intramolecular motions and the chemical exchange of the amino protons are inhibited. Compared to the studies at the ambient temperature, this approach allows us to extract more distance restraints for the use in the molecular dynamics calculations.

       A series of the 2D-NOESY spectra with the mixing times in a range of 50 to 400 ms has been measured at 268K. The assignment of the spectra revealed 11 of 14 assigned amino proton resonances compared to 6 of 14 resonances extracted at 298K. The NOESY cross-peaks for the different mixing times were integrated using the SPARKY program and the results were employed to derive the inter-proton distance restraints. Our treatment of the NOESY cross-peak volumes includes both the Isolated Spin Pair Approach (ISPA) and the relaxation matrix approach represented by the MARDIGRAS and MORASS algorithms in order to account for the spin diffusion. The choice of the method for the extraction of a sufficiently large number of accurate proton distances from 2D NOE  cross-peak intensities may be important for the subsequent structure calculations. Here we compare the NOE-derived interproton distances obtained by the ISPA and the relaxation matrix analyses for several sets of experimental data.

 

 

1.    P. Padrta, R. Štefl, L. Králík, L. Žídek, V. Sklenář, J. Biomol. NMR, 24, (2002), 1 - 14

2.    U. Schmitz, D. A. Pearlman, T. L. James, J. Mol. Biol., 221, (1991), 271 292