Relationship of DNA structure to internal dynamics: Correlation of helicalparameters from NOE-based NMR solution structures of d(GCGTACGC)(2) and d(CGCTAGCG)(2) with C-13 order parameters implies conformational coupling in dinucleotide units

The coupling between the conformational properties of double-stranded DNA a nd its internal dynamics has been examined. The solution structures of the isomeric DNA oligomers d(GCGTACGC)(2) (UM) and d(CGCTAGCG)(2) (CTSYM) were determined with H-1 NMR spectroscopy by utilizing distance restraints from total relaxation matrix analysis of NOESY cross-peak intensities in restrai ned molecular dynamics calculations. The root-mean-square deviation of the coordinates for the ensemble of structures was 0.13 Angstrom for UM and 0.4 9 Angstrom for CTSYM, with crystallographic equivalent R-c=0.41 and 0.39 an d sixth-root residual R-x=0.11 and 0.10 for UM and CTSYM, respectively. Bot h UM and CTSYM. are B-form with straight helical axes and show sequence-dep endent variations in conformation. The internal dynamics of UM and CTSYM we re previously determined by analysis of C-13 relaxation parameters in the c ontext of the Lipari & Szabo model-free formalism. Helical parameters for t he two DNA oligomers were examined for linear correlations with the order p arameters (S-2) of groups of C-13 spins in base-pairs and dinucleotide unit s of UM and CTSYM. Correlations were found for six interstrand base-pair pa rameters tip, y-displacement, inclination, buckle and stretch with various combinations of S-2 for atoms in Watson-Crick base-pairs and for two inter- base-pair parameters, rise and roll with various combinations of S-2 for at oms in dinucleotides. The correlations for the interstrand base-pair helica l parameters indicate that the conformations of the deoxyribose residues of each strand are dynamically coupled. Also, the inter-base-pair separation has a profound effect on the local internal motions available to the DNA, s upporting the idea that rise is a principal degree of freedom for DNA confo rmational variability. The correlations indicate collective atomic motions of spins that may represent specific motional modes in DNA, and that base s equence has a predictable effect on the relative order of groups of spins b oth in the bases and in the deoxyribose ring of the DNA backbone. These obs ervations suggest that an important functional outcome of DNA base sequence is the modulation of both the conformation and dynamic behavior of the DNA backbone. (C) 2001 Academic Press.