A refined prediction method for gel retardation of DNA oligonucleotides from dinucleotide step parameters: Reconciliation of DNA bending models with crystal structure data

The development and assessment or a prediction method for gel retardation a nd sequence dependent curvature of DNA based on dinucleotide step parameter s are described. The method is formulated using the Babcock-Olson equations for base pair step geometry ii) and employs Monte Carte simulated annealin g for parameter optimization against experimental data. The refined base pa ir step parameters define a structural construct which, when the width of o bserved parameter distributions is taken into account, is consistent with t he results of DNA oligonucleotide crystal structures. The predictive power of the method is demonstrated and rested via comparisons with DNA bending d ata on sets of sequences not included in the training set, including A-trac ts with and without periodic helix phasing, phased A(4)T(4) and T(4)A(4) mo tifs, a sequence with a phased GGGCCC motif, some "unconventional" helix ph asing sequences, and three short fragments of kinetoplast DNA from Crithidi a fasiculata that exhibit significantly different behavior on non-denaturin g polyacrylamide gels. The nature of the structural construct produced by t he methodology is discussed with respect to static and dynamic models of st ructure and representations of bending and bendability. An independent theo retical account of sequence dependent chemical footprinting results is prov ided. Detailed analysis of sequences with A-tract induced axis bending form s the basis for a critical discussion of the applicability of wedge models, junction models and non A-tract, general sequence models for understanding the origin of DNA curvature at the molecular level.