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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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Representative dependence of the effective force (red) and the free energy (black) of two axially aligned DNA fragments on the end-to-end distance. The data result from 100 independent simulations of two 5′-phosphorylated fragments, the end-to-end distance of which was maintained at a specified value by a harmonic spring. Additional restraints were applied to maintain the axial alignment. The strength of the restraints was found to affect the values but not the general shape of both curves (see text). The image in the background illustrates the simulation method. The DNA fragments were immersed in 100 mM NaCl electrolyte, and were free to rotate about their helical axes.
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gkr1220-F3: Representative dependence of the effective force (red) and the free energy (black) of two axially aligned DNA fragments on the end-to-end distance. The data result from 100 independent simulations of two 5′-phosphorylated fragments, the end-to-end distance of which was maintained at a specified value by a harmonic spring. Additional restraints were applied to maintain the axial alignment. The strength of the restraints was found to affect the values but not the general shape of both curves (see text). The image in the background illustrates the simulation method. The DNA fragments were immersed in 100 mM NaCl electrolyte, and were free to rotate about their helical axes.

Mentions: Umbrella sampling simulations were performed using the anisotropic systems (Figure 1a) and two simulation protocols different by the method used to set up initial systems and the alignment restraints. Both protocols enforced the end-to-end distance r using a harmonic spring of ks = 4000 pN/nm for 3.5 < r < 12 Å in 0.5-Å intervals and ks = 1000 pN/nm for 13 < r < 19 Å in 1.0-Å intervals. The first protocol was used to provide the estimate of the potential of mean force (PMF) (Figure 3). The initial conformation for each simulation was obtained by placing the DNA fragments a specified distance r apart at one of the four ϕ = 0, 90, 180 and 270° (four simulations for each r). The systems were equilibrated for 2 ns before data accumulation during production simulations lasting ∼16 ns. In the second protocol, which we used to compute the relative binding free energies (Table 1), the initial conformations were generated iteratively by shifting the minimum of the restraining potential in steps and followed by 0.5-ns equilibration, starting from the final frames obtained in the simulations described in the section ‘Collapse of aligned dsDNA’. Subsequently, each system was equilibrated for at least 2.5 ns before accumulation of data during production simulations lasting 7.5–15 ns. Axial alignment was maintained as described in the section “Collapse of aligned dsDNA”, using ks = 13.9 and 139 pN/nm for the first and second protocols, respectively. In the second protocol, a torque pointing along the common DNA axis was distributed among the phosphorous atoms of each DNA molecule to restrain ϕ about −20°, 36° or 180°, with a spring constant of 219.4 pN nm/rad2, which roughly corresponds to an 8° root mean squared fluctuation.Figure 3.


End-to-end attraction of duplex DNA.

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

Representative dependence of the effective force (red) and the free energy (black) of two axially aligned DNA fragments on the end-to-end distance. The data result from 100 independent simulations of two 5′-phosphorylated fragments, the end-to-end distance of which was maintained at a specified value by a harmonic spring. Additional restraints were applied to maintain the axial alignment. The strength of the restraints was found to affect the values but not the general shape of both curves (see text). The image in the background illustrates the simulation method. The DNA fragments were immersed in 100 mM NaCl electrolyte, and were free to rotate about their helical axes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkr1220-F3: Representative dependence of the effective force (red) and the free energy (black) of two axially aligned DNA fragments on the end-to-end distance. The data result from 100 independent simulations of two 5′-phosphorylated fragments, the end-to-end distance of which was maintained at a specified value by a harmonic spring. Additional restraints were applied to maintain the axial alignment. The strength of the restraints was found to affect the values but not the general shape of both curves (see text). The image in the background illustrates the simulation method. The DNA fragments were immersed in 100 mM NaCl electrolyte, and were free to rotate about their helical axes.
Mentions: Umbrella sampling simulations were performed using the anisotropic systems (Figure 1a) and two simulation protocols different by the method used to set up initial systems and the alignment restraints. Both protocols enforced the end-to-end distance r using a harmonic spring of ks = 4000 pN/nm for 3.5 < r < 12 Å in 0.5-Å intervals and ks = 1000 pN/nm for 13 < r < 19 Å in 1.0-Å intervals. The first protocol was used to provide the estimate of the potential of mean force (PMF) (Figure 3). The initial conformation for each simulation was obtained by placing the DNA fragments a specified distance r apart at one of the four ϕ = 0, 90, 180 and 270° (four simulations for each r). The systems were equilibrated for 2 ns before data accumulation during production simulations lasting ∼16 ns. In the second protocol, which we used to compute the relative binding free energies (Table 1), the initial conformations were generated iteratively by shifting the minimum of the restraining potential in steps and followed by 0.5-ns equilibration, starting from the final frames obtained in the simulations described in the section ‘Collapse of aligned dsDNA’. Subsequently, each system was equilibrated for at least 2.5 ns before accumulation of data during production simulations lasting 7.5–15 ns. Axial alignment was maintained as described in the section “Collapse of aligned dsDNA”, using ks = 13.9 and 139 pN/nm for the first and second protocols, respectively. In the second protocol, a torque pointing along the common DNA axis was distributed among the phosphorous atoms of each DNA molecule to restrain ϕ about −20°, 36° or 180°, with a spring constant of 219.4 pN nm/rad2, which roughly corresponds to an 8° root mean squared fluctuation.Figure 3.

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