End-to-end attraction of duplex DNA

Abstract

Recent experiments [Nakata, M. et al., End-to-end stacking and liquid crystal condensation of 6 to 20 basepair DNA duplexes. Science 2007; 318:1276–1279] have demonstrated spontaneous end-to-end association of short duplex DNA fragments into long rod-like structures. By means of extensive all-atom molecular dynamic simulations, we characterized end-to-end interactions of duplex DNA, quantitatively describing the forces, free energy and kinetics of the end-to-end association process. We found short DNA duplexes to spontaneously aggregate end-to-end when axially aligned in a small volume of monovalent electrolyte. It was observed that electrostatic repulsion of 5′-phosphoryl groups promoted the formation of aggregates in a conformation similar to the B-form DNA double helix. Application of an external force revealed that rupture of the end-to-end assembly occurs by the shearing of the terminal base pairs. The standard binding free energy and the kinetic rates of end-to-end association and dissociation processes were estimated using two complementary methods: umbrella sampling simulations of two DNA fragments and direct observation of the aggregation process in a system containing 458 DNA fragments. We found the end-to-end force to be short range, attractive, hydrophobic and only weakly dependent on the ion concentration. The relation between the stacking free energy and end-to-end attraction is discussed as well as possible roles of the end-to-end interaction in biological and nanotechnological systems.

Understanding the origin of liquid crystal ordering of ultrashort double-stranded DNA

“…In a simulation of two axially aligned DNA fragments kept a small distance apart, we observe a very swift approach and stacking in the FH configuration at a distance of 3.75Å validating the above observations ( Figure S3A-B) [33]. Our binding energy values are consistent with the value (6.3 kcal/mol) obtained by Aksimentiev et al [44] for the end-to-end stacking of 10-bp long dsDNA which were free to rotate about their common axis contrary to ours. Being free to rotate, the azimuthal sampling of their DNA fragments and hence the accessibility of the interfacial bases to water due to thermal uctuations is in-between the two congurations that we have used, resulting in an intermediate value of binding energy.…”

“…al. [44] in their study using atomistic simulation, also found two preferential values for the azimuthal angle. De Michele et al [57] find the peak for end-to-end distance distribution at around 3.7 A, while, Maffeo et al [44] report peak at around 5Å.…”

“…[44] in their study using atomistic simulation, also found two preferential values for the azimuthal angle. De Michele et al [57] find the peak for end-to-end distance distribution at around 3.7 A, while, Maffeo et al [44] report peak at around 5Å. The difference is attributed to the higher salt concentration of the system studied by De Michele et al In the present study we obtain the peak at 3.7Å eventhough the salt concentration is set to zero.…”

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

“…Classical all-atom approaches, where every atom of DNA and the surrounding solvent is modelled as a point particle with effective interactions, have been widely employed to study small DNA motifs 14,15 and have recently been applied to larger DNA systems. [16][17][18] However, simulating rare-event processes such as the breaking or formation of base pairs remains a challenge with these models, with µs time scales being the limit of what is currently accessible. 18 At the other end of the scale, theoretical approaches have been developed to understand certain large-scale properties of DNA.…”

Liquid Crystal Ordering of Four-Base-Long DNA Oligomers with Both G–C and A–T Pairing

“…The effect of EtBr might also be related to the absence in GCTA of the terminal phosphate, which is instead present in the other two molecules. Atomistic computer simulations have suggested that DNA stacking interactions in presence of phosphate terminal is stronger and more constraining to the natural helical continuity [21]. Thus, it could be argued that the presence of EtBr in GCTA has a more relevant role in stabilizing the interaction across the adjacent coaxially stacked strands, which is in this case weaker because of the absence of phosphate termination.…”