A Coarse-Grained Simulation Study of the Effect of Salt Concentration on DNA Internal Motions

Abstract

Earlier studies by Chow and Skolnick suggest that the internal motions of bacterial DNA appear to be governed by strong forces arising from being crowded into the small spacing of the nucleoid. However, the effect of ion concentration on the internal motions of densely packed DNA is not well understood. For this study, we built and used a program called ‘BDT’ for Brownian dynamics (BD) simulations of DNA using the free-draining approximation. While it performs BD simulations with steric, stretch, bend, and Debye-Huckel forces, BDT also introduces routines that have been optimized for DNA chain calculations. A fractal DNA chain was prepared using a custom program, which arranged DNA beads along a Hilbert space-filling curve where straight segments were at least twice the persistence length of DNA. The simulation box was slowly reduced in volume until the in vivo DNA volume fraction of ∼13% was reached. BD simulations using this initial configuration were carried out at ion concentrations from 0.0001M to 0.5M, and a separate simulation was performed in the absence of Debye-Huckel forces. Diffusion constants and DNA internal motions were studied over increasing ion concentrations. The results suggest that the diffusion activity of DNA increases to a limit with increases in ion concentration. Furthermore, the diffusion values obtained from a simulation of DNA near cellular conditions of 0.1M appear to be close to those obtained from simulations in which Debye-Huckel interactions were absent. This implies that the computation of Debye-Huckel interactions may actually be unnecessary in BD simulations of DNA motion under in vivo conditions, where other forces dominate DNA motion, and that BD simulations of similar conditions can benefit in computational efficiency from the removal of this calculation with minimal loss of simulation fidelity.