Abstract
Computer modeling of very large biomolecular systems, such as long DNA polyelectrolytes or protein-DNA complex-like chromatin cannot reach all-atom resolution in a foreseeable future and this necessitates the development of coarse-grained (CG) approximations. DNA is both highly charged and mechanically rigid semi-flexible polymer and adequate DNA modeling requires a correct description of both its structural stiffness and salt-dependent electrostatic forces. Here, we present a novel CG model of DNA that approximates the DNA polymer as a chain of 5-bead units. Each unit represents two DNA base pairs with one central bead for bases and pentose moieties and four others for phosphate groups. Charges, intra- and inter-molecular force field potentials for the CG DNA model were calculated using the inverse Monte Carlo method from all atom molecular dynamic (MD) simulations of 22 bp DNA oligonucleotides. The CG model was tested by performing dielectric continuum Langevin MD simulations of a 200 bp double helix DNA in solutions of monovalent salt with explicit ions. Excellent agreement with experimental data was obtained for the dependence of the DNA persistent length on salt concentration in the range 0.1–100 mM. The new CG DNA model is suitable for modeling various biomolecular systems with adequate description of electrostatic and mechanical properties.
Highlights
During decades, the DNA molecule has been studied in a vast number of experimental, theoretical, and modeling research investigations
In order to facilitate their use in general purpose molecular dynamics software, we approximated the internal bond and angle potentials of DNA by harmonic functions
We present a CG DNA model that consist of two types of beads representing a set of two base pairs, one P bead for each phosphate group and one central D bead for the pentose and bases of a two-bp unit (Figure 1)
Summary
The DNA molecule has been studied in a vast number of experimental, theoretical, and modeling research investigations. The study of polyelectrolyte properties of DNA takes an important place in these works since electrostatic interactions and salt effects have a profound influence on many other DNA properties and interactions of DNA with its surrounding. The problem of polyelectrolyte and DNA condensation in solution has a long history of experimental studies [5,6]. In order to model and describe the folding and aggregation of chromatin, Poisson-Boltzmann based models, including the popular Debye-Hückel type approaches [13,14,15], have serious limitations which may be a source of artefacts in predictions of aggregation properties. The reason is that such models do not include effects due to the explicit presence of mobile ions and do not take into account the molecular nature of the solvent
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