(211a) Unraveling the Dynamics of Supercoiled DNA with Theoretical Modeling

In many instances in Nature and in biotechnology applications, DNA is either in a closed-circular, plasmid form or a topologically closed state; both cases exhibit supercoiling when sufficiently twisted. The class of enzymes called topoisomerases control the degree of supercoiling and are implicated in a number of biological processes. The ability of the cell to control DNA supercoiling is essential for cell survival, and disruption of topoisomerase activity leads to genetic instability and alteration of protein expression. As such, the supercoiling of DNA plays a pivotal role in the function of DNA, impacting a wide range of biological processes.

This research project represents a systematic study of the dynamics of supercoiled DNA using theory and computation. We address the dynamics of structural transitions and site juxtaposition in supercoiled DNA, lending critical physical insight into the molecular dynamics of these fundamental processes. We utilize analytical predictions for the formation of loops in twisted filaments as a prediction of the rate of formation of supercoiled structures in plasmid DNA. Brownian dynamics simulations of plasmid DNA are performed in order to determine the dynamics of the restructuring of the supercoiled structures, using our analytical predictions for supercoil formation as guidance. We will discuss the impact of supercoiling dynamics on the kinetics of target-site localization of DNA-binding proteins.