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WIREs Comput Mol Sci

Recent successes in coarse‐grained modeling of DNA

Advanced Review

Davit A. Potoyan, Alexey Savelyev, Garegin A. Papoian

Published Online: Aug 08 2012

DOI: 10.1002/wcms.1114

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The growing interest in the DNA‐based mesoscale systems of biological and nonbiological nature has encouraged the computational molecular science community to develop coarse‐grained (CG) representationsof the DNA that will be simple enough to permit exhaustive simulations in a reasonable amount of time, yet complex enough to capture the essential physics at play. In the recent years, there have been some major developments in the DNA coarse‐graining area and several fairly sophisticated models are now available that faithfully reproduce key mechanical and chemical properties of the double‐ and single‐stranded DNA. However, there are still many challenges, which limit the applicability of the present models, and much has to be done yet to develop more reliable schemes which would have a predictive power beyond the target domain of the intrinsic parametrization. A development of robust, controllable, and transferrable CG DNA force fields will provide an invaluable tool for gaining physical insights into the molecular nature of complex DNA‐based nanoscale entities such as the chromatin, virus capsids, and DNA nanocomposites. In the present contribution, we provide an overview of the recent developments in the DNA coarse‐graining field. Our aim is to review the existing CG models of the double‐stranded DNA, where a small selection of models, which we believe provide avenues for promising future development, are discussed in some detail. © 2012 John Wiley & Sons, Ltd.

Figure 1.

A discrete model of a hypothetical polymer drawn to illustrate the worm‐like chain (WLC) model. The i and j denote the indices for beads and a is the diameter of the bead. The upper part of the figure shows three regimes predicted by the WLC model. (a) The coil regime where the chain is governed by the conformational entropy and assumes random‐like configurations; (b) semiflexible regime, where chain has occasional small kinks along the contour but is overall aligned in one direction; (c) rod limit, where the chain can be effectively regarded as a straight line.

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Figure 2.

(a) Schematic representation of the mesoscale model of DNA (b) Comparison of thermal melting curves from the coarse‐grained simulations with the experiments. (Reprinted with permission from Ref 59. Copyright 2007 AIP.)

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Figure 3.

(a) Schematic representation of three nucleotides, with ellipsoidal beads corresponding to bases and the beads labeled as S and P to sugars and phosphate groups, respectively. (b) The all atom framework of nucleic base, showing the principal axes of the ellipsoid, which uniquely determine the orientation of the base. (Reprinted with permission from Ref 37. Copyright 2010 AIP.)

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Figure 4.

A recently developed chemically accurate coarse‐grained model of the double‐stranded DNA with explicit mobile ions by Savelyev and Papoian.2 Each DNA base‐pair is represented by two beads, each placed in the geometric center of the corresponding atomistic nucleotide. Blue dashed lines indicate effective interactions which represent a superposition of stacking and base pairing among two polynucleotides.

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Figure 5.

Recent applications of the CG DNA model by Savelyev and Papoian. (a) The model was used to measure DNA persistence length in a wide range of NaCl concentrations, covering three order of magnitudes; computational results appeared to be in quantitative agreement with experimental data. (Graphs are taken from Ref 2.) (b) The model was employed in a study of the behavior of DNA–nanosphere complex mimicking nucleosome core particle72; typical MD simulation snapshots demonstrate nucleosomal wrapping (taken from Ref 72). (c) The model predicts a pronounced phase transition to a buckled state in the overtwisted 90‐base‐pair DNA nanocircle at physiological concentrations of NaCl salt buffer (taken from Ref 2).

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