A Coarse-Grained Model of DNA with Explicit Solvation by Water and Ions

RC DeMille and TE Cheatham and V Molinero, JOURNAL OF PHYSICAL CHEMISTRY B, 115, 132-142 (2011).

DOI: 10.1021/jp107028n

Solvation by water and ions has been shown to be vitally important for biological molecules, yet fully atomistic simulations of large biomolecules remain a challenge due to their high computational cost. The effect of solvation is the most pronounced in polyelectrolytes, of which DNA is a paradigmatic example. Coarse-grained (CO) representations have been developed to model the essential physics of the DNA molecule, yet almost without exception, these models replace the water and ions by implicit solvation in order to significantly reduce the computational expense. This work introduces the first coarse-grained model of DNA solvated explicitly with water and ions. To this end, we combined two established CO models; the recently developed mW-ion model DeMille, R. C.; Molinero, V. J. Chem. Phys. 2009, 131, 0341071, which reproduces the structure of aqueous ionic solutions without electrostatic interactions, was coupled to the three-sites-per-nucleotide (3SPN) CO model of DNA Knotts, T. A., IV; et al. J. Chem. Phys. 2007, 126, 084901. Using atomistic simulations of d(CGCGAATTCGCG)(2) as a reference, we optimized the coarse-grained interactions between DNA and solvent to reproduce the solvation structure of water and ions around CO DNA. The resulting coarse-grained model of DNA explicitly solvated by ions and water (mW/3SPN-DNA) exhibits base-pair specificity and ion-condensation effects and it is 2 orders of magnitude computationally more efficient than atomistic models. We describe the parametrization strategy and offer insight into how other CO models may be combined with a coarse- grained solvent model such as mW-ion.