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 <i>in vivo</i> at a given time, and the crowded environment they inhabit. The fast association between proteins and DNA is governed by nonspecific interactions that allow protein sliding along DNA where the protein binds DNA nonspecifically and performs a helical motion when it is placed in the major groove. We have explored using various computational approaches 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. Protein sliding may occur on single-stranded DNA as well, yet via a different mechanism than that for double-stranded DNA. Furthermore, the interaction between proteins and DNA also has to result with high affinity complexes. In my presentation, I will discuss the molecular features of proteins and of the nucleic acids that allow fast dynamics and high affinity binding on both single- and double-stranded DNA.

Molecular principles for optimizing protein-DNA interactions

253rd National Meeting (2017)

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