Interactions between proteins and nucleic acids are ubiquitous and central to the life of cells. The remarkable efficiency and specificity of protein-DNA recognition presents a major theoretical puzzle given the size of the genome, the large number of molecular species in vivo at a given time, and the crowded environment they inhabit. Our research is motivated at quantitatively advancing our understanding of the kinetics and mechanisms of protein-DNA recognition, the molecular and physical principles of fast association, and protein recruitment by DNA. For the first time, we have visualized protein sliding along DNA where the protein binds DNA nonspecifically and performs a helical motion when it is placed in the major groove. Using coarse-grained models we found that the spiral motion along the sugar-phosphate rail is typical to various DNA-binding motifs. This stochastic dynamics that is governed by electrostatic forces has similar structural features to the specific binding mode of the protein with the DNA. In our study, we address the question of the linkage between the molecular architecture of DNA-binding proteins and the search mechanism. We have explored the interplay between the molecular characteristics of the proteins (e.g., DNA recognition motifs, degree of flexibility, and oligomeric states) and the nature of sliding, intersegment transfer events and the overall efficiency of the DNA search. Another important aspect of the search is how the in-vivo conditions (for example, crowding in the cell or coverage of DNA by nucleosomes) affect the efficiency of DNA search.

Dynamics of DNA search using sliding and jumping: A molecular perspective

244th National Meeting (2012)

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