A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

Abstract

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.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

“…Many coarse-grained DNA models have been developed in recent years; [20][21][22][23][24][25][26][27][28][29] in this work, we improve the model due to Ouldridge et al, oxDNA. 30,31 This nucleotide-level model is designed with a heuristic, "top-down" approach, with a focus on reproducing well-known properties of DNA (such as the helical structure of the B-DNA duplex) and experimental results (such as duplex melting temperatures), rather than, for example, building the model up by integrating out details from an all-atom representation.…”

Multiscale simulation of DNA

“…Most of the successful CG models use from 2 (oxDNA [135][136][137][138], and Aksim nti v's m d l [148]), or 3 (3SPN [131][132][133]139,140], BioModi [149]), to eight beads per nucleotide (see Figure 2, and Table 1 for more details). However, coarser models with five beads per base-pair step (four nucleotides), or even a single bead per nucleotide have emerged [126,127]. When more than one bead is used, all the models have chosen to place the beads in order to reproduce the position and connectivity existing between the backbone, the sugar puckering and the base (Figure 2).…”

“…Only a few models incorporate electrostatic explicitly [127,128,130,141•] assigning partial charges to the DNA beads, but in all the cases the environment around DNA has been taken into account at some degree, by using implicit or explicit approaches. Most models used implicit Langevin dynamics (with increased viscosity of the medium) coupled to the Debye-Hückel approach (when electrostatics is explicitly taken into account) to treat the ionic strength (Table 1).…”

“…In this regard, several coarse-grained models were applied to understand certain processes of biological interest, like duplex formation starting from short ssDNA oligomers [127,131,132,142]. Other models have shown to be useful in reproducing the structure of DNA/RNA duplexes [129], or structural properties such as the sequencedependent/salt-dependent persistence length [127,131,132], or the DNA curvature. The model from Vercauteren and coworkers was able to reproduce the topology of several DNA mini-circles with different link numbers, simulated using explicit K + Cl -ions [126].…”

Optimization of a Nucleic Acids united-RESidue 2-Point model (NARES-2P) with a maximum-likelihood approach

“…These molecules would be too large to simulate using an all-atom force field, even with Anton. 8 Therefore, coarse-grained force fields for nucleic acids [9][10][11][12][13][14][15][16][17][18][19][20] are playing an important role in simulating nucleic acids in recent years.…”