DNA-Conformations and its Role in Sequence Recognition

The readout of structural information of DNA by proteins or small ligands is of extraordinary biological interest. It can be achieved either by direct or by indirect readout. Indirect readout explains how the sequence information of DNA can be read without building specific contacts to the bases. It is mediated on the one hand by the sequence specific energetic penalty which is needed to disturb the DNA from its low energy conformation of the unbound state, and on the other hand by contacts with the non-specific part of the DNA. The non-specific part of the DNA is mainly formed by its sugar-phosphate backbone. Although this backbone is chemically degenerate recent results propose that it contains sequence information encoded in its backbone conformation. Thus the exact understanding of the DNA backbone conformation behavior is necessary in order to deepen our insight into sequence recognition of DNA. During my Ph.D I performed computer simulations concerning the field of DNA backbone conformations leading to interesting results. The future aim is to design ligands which influence the protein binding by their effect on the backbone. Starting from the results of my Ph.D thesis I plan further research by means of nuclear magnetic resonance and molecular modelling. This combination of NMR and molecular modelling techniques has already proven their capability to gain detailed information about the backbone. Therefore this research could lead to new insight into the exact behavior of the DNA backbone and additionally I would learn new experimental techniques helpful for my future scientific career.