Solution structure of [d(A-T)5]2 via complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect spectra and molecular mechanics calculations: evidence for a hydration tunnel.

Pure absorption phase proton two-dimensional nuclear Overhauser effect (2D NOE) spectra at 500 MHz have been obtained for [d(5'ATATATATAT3')]2 in deuterium oxide solution at several mixing times. The 100 nonexchangeable proton resonances have been assigned. The experimental 2D NOE spectra were compared with theoretical spectra calculated by using the complete relaxation matrix analysis method [Keepers, J. W., & James, T. L. (1984) J. Magn. Reson. 57, 404-426] and x-ray diffraction determined molecular coordinates of A, B, alternating B, left-handed B, C, D, and wrinkled D forms of DNA and of energy-minimized structures calculated from the most promising X-ray crystal structures by using the molecular mechanics program AMBER, in which all hydrogens, counterions, and hydration water molecules were included. The analysis of all features of the 2D NOE spectra played an important role in extracting the promising structures, and it was concluded that the wrinkled D form yields the best fit for the 2D NOE data of the A-T decamer. The molecular mechanics calculation indicated that this model structure, whose minor groove is comparatively deep and narrow, may be energetically more stable than the B form for alternating d(A-T) DNA. Interesting features of the structure include possible intra- and interchain sugar-phosphate attractions and a hydration tunnel inside the minor groove capable of accommodating three types of water molecules that aid in helix stabilization via hydrogen bonding. Counterions (sodium) serve to reduce interchain phosphate-phosphate repulsive effects.