The three-dimensional structure in solution (pH 5.8) of a DNA 9-mer duplex containing 1,N2-propanodeoxyguanosine opposite deoxyadenosine. Restrained molecular dynamics and NOE-based refinement calculations.

The solution structure of the complementary d(C1-A2-T3-G4-X5-G6-T7-A8-C9).d(G10-T11-A12-C13-A14-C15-A 16-T17-G18) nonanucleotide duplex (designated X.A 9-mer) that contains a 1,N2-propanodeoxyguanosine exocyclic adduct, X5, opposite deoxyadenosine A14 in the center of the helix at pH 5.8 is investigated by use of restrained molecular dynamics followed by NOE-based back-calculation refinement. The molecular dynamics calculation is based on 91 interresidue and 97 intraresidue interproton distance restraints derived from two-dimensional nuclear Overhauser enhancement data on the X.A 9-mer at mixing times of 50 and 250 ms [Kouchakdjian, M., Marinelli, E., Gao, X., Johnson, F., Grollman, A., & Patel, D.J. (1989) Biochemistry 28, 5647-5657]. Separate runs start from classical A and B DNA and converge to essentially identical structures (atomic root mean square difference of 0.69 A). Both structures are B-type DNA in character and satisfy the experimental distance restraints with the rms difference of only 0.001 A between the calculated and experimental interproton distances. The dynamics behavior of the A----B DNA transition is monitored and analyzed. Our results clearly indicate that the driving force of the convergence is the experimental interproton distance restraints. The molecular dynamics structures are further refined by a back-calculation dynamics which directly minimizes the difference between the observed 2D NOE intensities and those calculated by the full relaxation matrix approach. The fit of the refined structures to the NOE intensities is measured by the NOE R value, which is analogous to the crystallographic residual index. These R values of the final structures are only 0.17. The refined structures are generally B type, and their convergency improves slightly to an atomic root mean square difference of 0.64 A, despite relatively large structural shifts (approximately 1 A) which occur during the back-calculation refinement in both cases. These results suggest that the converged refined structures represent reasonable approximations of the solution structure.