Sequence-dependent Kink-and-Slide Deformations of Nucleosomal DNA Facilitated by Histone Arginines Bound in the Minor Groove

To understand the sequence dependence of such Kink-and-Slide deformations, we performed allatom calculations of DNA hexamers with the YR and RY steps in the center. We found that when the unrestrained DNA deformations are allowed, the YR steps tend to bend into the major groove, and RY steps bend into the minor groove. However, when the nucleosomal Kink-and-Slide deformation is considered, the YR steps prove to be more favorable for bending into the minor groove. Overall, the Kink-and-Slide deformation energy of DNA increases in the order TA < CA < CG < GC < AC < AT. We propose a simple stereochemical model accounting for this sequence dependence. Our results agree with experimental data indicating that the TA step most frequently occurs in the minor-groove kink positions in the most stable nucleosomes. Our computations demonstrate that the Kink-and-Slide distortion is accompanied by the BI to BII transition. This fact, together with irregularities in the two-dimensional (Roll, Slide) energy contour maps, suggest that the Kink-and-Slide deformations represent a nonharmonic behavior of the duplex. This explains the difference between the two estimates of the DNA deformation energy in nucleosome – the earlier one made using knowledge-based elastic energy functions, and the current one based on all-atom calculations. Our findings are useful for refining the score functions for the prediction of nucleosome positioning. In addition, the reverse bending behavior of the YR and RY steps revealed under the Kink-and-Slide constraint is important for understanding the molecular mechanisms of binding transcription factors (such as p53) to DNA exposed on the surface of nucleosome.