Diffusion-controlled intrachain reactions of supercoiled DNA: Brownian Dynamics simulations

The Brownian Dynamics technique was used to model a diffusion-controlled intramolecular reaction of supercoiled DNA (2500 basepairs) in 0.1 M sodium chloride solution. The distance between the reactive groups along the DNA contour was 470 basepairs. The reaction radius was varied from 6 to 20 nm. The results are presented in terms of the probability distribution P(F)(t) of the first collision time. The general form of the function P(F)(t) could be correctly predicted by a simple analytical model of one-dimensional diffusion of the superhelix ends along the DNA contour. The distribution P(F)(t) is essentially non-exponential: within a large initial time interval, it scales as P(F)(t) approximately t(-1/2), which is typical for one-dimensional diffusion. However, the mean time of the first collision is inversely proportional to the reaction radius, as in three dimensions. A visual inspection of the simulated conformations showed that a considerable part of the collisions is caused by the bending of the superhelix axis in the regions of the end loops, where the axis is most flexible. This fact explains why the distribution P(F)(t) combines the features of one- and three-dimensional diffusion. The simulations were repeated for a DNA chain with a permanent bend of 100 degrees in the middle position between the reactive groups along the DNA contour. The permanent bend changes dramatically the form of the distribution P(F)(t) and reduces the mean time of the first collision by approximately one order of magnitude.