Dynamic Force-Extension of DNA with Nucleoid Associated Proteins

Nucleoid associated proteins (NAPs) manipulate the genomic material in prokaryotic cells by manipulating the shape and structure of DNA. These NAPs act by bending or twisting DNA, and there are indications that the binding behavior of NAPs is dependent on the local bend of DNA. These interactions occur in a dynamic cell, where the forces acting on the DNA and the surrounding environment are changing. We predict that the different timescales will result in concentration and force dependent dynamic behaviors.
We use coarse-grained simulation of NAPs and DNA that allow us to study the dynamics of a single molecule system. The timescales of interest are the rate of DNA extension and the characteristic unbinding time of our model NAP. We are able to semi-quantitatively reproduce experimental force-extension curves. By pulling the DNA strand at different rates, we observe how the force behavior and NAP binding profiles change as a function of dynamic extension. At concentrations where there are large differences in the number of NAPs bound at equilibrium, more force is required to extend the DNA strand due to the local bends caused by NAPs. At high pulling rates, proteins do not have time to unbind, resulting in non-equilibrium association behavior which affects the measured force.