The Physics of DNA in Confinement

Abstract

Throughout all kingdoms of life, DNA is found to form compact structures. DNA is neatly wound inside a viral capsid, DNA forms hierarchical structures in cell nuclei, DNA could even be woven into complex 3D structures known as DNA origami. Such a ubiquitous compaction is surprising, as it contradicts, at the first look, the very basic physical properties of DNA: the high electrostatic charge and resistance to bending at the scale of 50 nm or less. Experimental work has shown that counterions surrounding DNA can considerably alter its properties, for example, turning electrostatic self-repulsion into attraction. Yet, elucidating the precise microscopic structure and mechanism of DNA-DNA interaction in confined environment remains beyond the experimental capability. Here, we report the results of all-atom molecular dynamics simulations that investigated the microscopic structure of dense DNA assemblies and the physics of interactions that makes such assemblies possible. First, we show that a refined parameterization of ion-DNA interaction [1] permits the all-atom MD method to quantitatively reproduce experimentally known properties [2,3] of dense DNA arrays. Next we characterize the microscopic structure of the arrays, elucidating their ionic atmosphere, preferred azimuthal orientation of DNA molecules, the pair-wise additivity of DNA-DNA forces, the longitudinal friction forces between DNA molecules, and the role of solvation force. Our study demonstrates the ability of all-atom molecular dynamics simulations to provide quantitative, accurate information about dense DNA systems, opening exciting opportunities for future work in the area of synthetic DNA nanostructures, DNA packaging in viral capsids and cell nuclei.[1] J Phys Chem Lett 3:45-50.[2] Proc Natl Acad Sci U S A 81:2621-2625.[3] Biophys J 94:4775-82.