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End-to-end attraction of duplex DNA.

Maffeo C, Luan B, Aksimentiev A - Nucleic Acids Res. (2012)

Bottom Line: We found short DNA duplexes to spontaneously aggregate end-to-end when axially aligned in a small volume of monovalent electrolyte.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Illinois at Urbana-Champaign, 1110 W. Green Street, Urbana, IL 61801, USA.

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.

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Stability of the end-to-end DNA assembly. (a) Simulation system containing two spatially unrestrained dsDNA fragments in 100 mM NaCl electrolyte. Both fragments are free to rotate and move about the simulation box. The system is drawn as in Figure 1a. An animation illustrating a typical MD trajectory is available in Supplementary Data. (b and c) End-to-end junction of 5′-phosphorylated dsDNA with ϕ=−20° (b) and blunt-ended dsDNA with ϕ=180° (c). (d and e) End-to-end distance (d) and relative azimuthal angle, ϕ, (e) of the DNA fragments in three unrestrained MD trajectories.
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gkr1220-F2: Stability of the end-to-end DNA assembly. (a) Simulation system containing two spatially unrestrained dsDNA fragments in 100 mM NaCl electrolyte. Both fragments are free to rotate and move about the simulation box. The system is drawn as in Figure 1a. An animation illustrating a typical MD trajectory is available in Supplementary Data. (b and c) End-to-end junction of 5′-phosphorylated dsDNA with ϕ=−20° (b) and blunt-ended dsDNA with ϕ=180° (c). (d and e) End-to-end distance (d) and relative azimuthal angle, ϕ, (e) of the DNA fragments in three unrestrained MD trajectories.

Mentions: Each simulation reported in this study used one of the following three system types: elongated along the z-axis to minimize the amount of solvent around two DNA fragments (∼24 000 atoms, Figure 1a); isotropic to allow two DNA fragments to tumble freely (∼56 000 atoms, Figure 2a); and large and isotropic to allow unbiased interaction between 458 DNA fragments (∼1.4 M atoms, Figure 4a). The DNA sequence was poly(dA·dT) in all systems. Counterions were added to each system to neutralize the DNA charge prior to the addition of a number of ions corresponding to the reported molarity (100 mM, except where specified) of NaCl electrolyte. Steric clashes that were introduced during the assembly of each system were removed from each system through minimization using a conjugate gradient method (27). Equilibration was performed in the NPT ensemble, and subsequent production simulations were performed in the NVT ensemble, except where specified.Figure 1.


End-to-end attraction of duplex DNA.

Maffeo C, Luan B, Aksimentiev A - Nucleic Acids Res. (2012)

Stability of the end-to-end DNA assembly. (a) Simulation system containing two spatially unrestrained dsDNA fragments in 100 mM NaCl electrolyte. Both fragments are free to rotate and move about the simulation box. The system is drawn as in Figure 1a. An animation illustrating a typical MD trajectory is available in Supplementary Data. (b and c) End-to-end junction of 5′-phosphorylated dsDNA with ϕ=−20° (b) and blunt-ended dsDNA with ϕ=180° (c). (d and e) End-to-end distance (d) and relative azimuthal angle, ϕ, (e) of the DNA fragments in three unrestrained MD trajectories.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351176&req=5

gkr1220-F2: Stability of the end-to-end DNA assembly. (a) Simulation system containing two spatially unrestrained dsDNA fragments in 100 mM NaCl electrolyte. Both fragments are free to rotate and move about the simulation box. The system is drawn as in Figure 1a. An animation illustrating a typical MD trajectory is available in Supplementary Data. (b and c) End-to-end junction of 5′-phosphorylated dsDNA with ϕ=−20° (b) and blunt-ended dsDNA with ϕ=180° (c). (d and e) End-to-end distance (d) and relative azimuthal angle, ϕ, (e) of the DNA fragments in three unrestrained MD trajectories.
Mentions: Each simulation reported in this study used one of the following three system types: elongated along the z-axis to minimize the amount of solvent around two DNA fragments (∼24 000 atoms, Figure 1a); isotropic to allow two DNA fragments to tumble freely (∼56 000 atoms, Figure 2a); and large and isotropic to allow unbiased interaction between 458 DNA fragments (∼1.4 M atoms, Figure 4a). The DNA sequence was poly(dA·dT) in all systems. Counterions were added to each system to neutralize the DNA charge prior to the addition of a number of ions corresponding to the reported molarity (100 mM, except where specified) of NaCl electrolyte. Steric clashes that were introduced during the assembly of each system were removed from each system through minimization using a conjugate gradient method (27). Equilibration was performed in the NPT ensemble, and subsequent production simulations were performed in the NVT ensemble, except where specified.Figure 1.

Bottom Line: We found short DNA duplexes to spontaneously aggregate end-to-end when axially aligned in a small volume of monovalent electrolyte.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, University of Illinois at Urbana-Champaign, 1110 W. Green Street, Urbana, IL 61801, USA.

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.

Show MeSH
Related in: MedlinePlus