DNA is one the best-recognized molecules. We are all familiar with the famous double-helix that carries instructions for manufacturing and assembling all the components of a living organism. But DNA is more than just a sequence of letters arranged on rigid ladder rungs; it is a polymer with unusual physical properties that, at times, appear to contradict one another. For example, DNA carries a large negative charge, yet under the right conditions, DNA molecules attract and condense into a compact state. The physical properties of DNA are broadly exploited by cells to perform the molecular feats neccessary for life including storage of information, replication and repair of that information, and regulataion of how that information is expressed. Hence, elucidation of the molecular mechanisms that govern the behavior of DNA in solution comprises a core thrust of our research.
Christopher Maffeo, Binquan Luan, and Aleksei Aksimentiev Nucleic Acids Res (2012)
DNA–DNA interactions are essential to many biological processes, including DNA replication, recombination and compaction. While side-by-side interactions between two or more DNA molecules have been the subject of many studies, end-to-end interaction of duplex DNA and its role in cell biology and DNA nanotechnology remains almost entirely unexplored. Recent experiments demonstrated spontaneous end-to-end association of short duplex DNA fragments into long rod-like structures. To determine the microscopic origin, magnitude and range of forces driving this spectacular self-assembly, we carried out the first direct study of end-to-end association using the all-atom molecular dynamics method. Our state-of-the-art free energy calculations combined with brute-force simulations of spontaneous self-assembly revealed the standard binding free energy and kinetic rate constants for the end-to-end interaction. We found the end-to-end force to be strong, short-range, hydrophobic and only weakly dependent on the ion concentration. The relation between the stacking free energy and end-to-end attraction was discussed as well as possible roles of the end-to-end interaction in biological and nanotechnological systems. This work is described in a report appearing in Nucleic Acids Research.
Christopher Maffeo, Robert Schöpflin, Hergen Brutzer, René Stehr, Aleksei Aksimentiev, Gero Wedemann, and Ralf Seidel Phys Rev Lett (2010)
DNA is so famously known as the carrier of genetic information that the structural and dynamical aspects of the molecule are often neglected. However, most cellular processes that involve DNA cannot be understood without consideration of its interactions with other DNA and proteins. Such interactions can give rise self-assembled structures, for example DNA supercoils, which we strive to understand using a bottom-up approach by examining the most basic constituents of a larger more complex system. Thus, in collaboration with the groups of Ralf Seidel at the University of Technology in Dresden and Gero Wedemann at the University of Applied Sciences Stralsund, we have examined the interactions between DNA helices in plectonemic supercoils using magnetic tweezers, coarse-grained Monte Carlo and atomistic molecular dynamics simulations. Building on our previous work, our group characterized the effective forces between parallel DNA in monovalent electrolytes at different ion concentrations. Our simulations revealed that the force between the DNA molecules is much smaller than that predicted by the Debye-Hückel cylinder model and that continuum models fail to describe DNA electrostatics. We further demonstrate that DNA-DNA interactions in monovalent electrolyte are well described using this simple cylinder model provided a significant charge adaptation factor is employed. Application of this model in coarse-grained Monte Carlo simulations provided results in excellent agreement with experimentally obtained results over a wide range of concentrations. This work is described in a report that appeared in Physical Review Letters.
Binquan Luan, and Aleksei Aksimentiev J Am Chem Soc (2008)
The dependence of the effective force on the distance between two DNA molecules was directly computed from a set of extensive all-atom molecular dynamics simulations. The simulations revealed that in a monovalent electrolyte the effective force is repulsive at short and long distances but can be attractive in the intermediate range. This attractive force is, however, too weak (approximately 5 pN per turn of a DNA helix) to induce DNA condensation in the presence of thermal fluctuations. In divalent electrolytes, DNA molecules were observed to form a bound state, where Mg(2+) ions bridged minor groves of DNA. The effective force in divalent electrolytes was predominantly attractive, reaching a maximum of 42 pN per one turn of a DNA helix.