Fine-tuning the DNA conductance by intercalation of drug molecules

In this work we study the structure-transport property relationships of small ligand intercalated DNA molecules using a multiscale modeling approach where extensive ab initio calculations are performed on numerous MD-simulated configurations of dsDNA and dsDNA intercalated with two different intercalators, ethidium and daunomycin. DNA conductance is found to increase by one order of magnitude upon drug intercalation due to the local unwinding of the DNA base pairs adjacent to the intercalated sites, which leads to modifications of the density of states in the near-Fermi-energy region of the ligand–DNA complex. Our study suggests that the intercalators can be used to enhance or tune the DNA conductance, which opens new possibilities for their potential applications in nanoelectronics.

Figure 1

Structural parameters of a bare 8- and 12-bp dsDNA and the same dsDNA with an ethidium or a daunomycin intercalated between the middle two base pairs. The height of the bars represents the average value of the parameters, while the error bars denote their standard deviation calculated using the last 50 ns of the 200-ns-long trajectory.

Figure 2

Atomic structure and intercalated arrangement of (a) ethidium (blue colored) and (b) daunomycin (green colored) between two base pairs (shown in VDW representation). Schematic representations showing the charge transport setup and structure of (c) bare dsDNA: two strands shown in green and red color, respectively, and (d) ethidium-intercalated dsDNA: the ethidium (blue colored) intercalated between two base pairs of dsDNA. The virtual gold electrodes are shown as yellow spheres, while water molecules and ions are not shown here for clarity. (e) Transmission probability curve for the DNA and drug-DNA complexes (averaged over 75 morphologies) in the region close to the Fermi energy for 8-bp dsDNA sequence with and without intercalators. (f) $V-I$ characteristic curves of 8-bp dsDNA with and without intercalators. (g) Distribution of the log of current at an applied potential of 100 mV for bare dsDNA and intercalated dsDNA. The intercalated dsDNA has a higher number of snapshots for larger current value than the bare dsDNA. (h) Density of states for the 8-bp dsDNA in the presence and absence of an intercalator computed using the energy states of all 75 morphologies studied for each case. The inset shows the zoomed-view DOS in the positive side of the Fermi energy region.

Figure 3

(a) $V-I$ characteristic curves of 12-bp dsDNA with and without intercalators. Clearly, the current increases by orders of magnitude upon intercalation. (b) Transmission probability curve in the near-Fermi-energy region for 12-bp dsDNA sequence with and without intercalators. (c) Density of states for 12-bp dsDNA. Clearly, intercalated dsDNA has a lower HOMO-LUMO gap relative to the normal dsDNA. Due to this, the transmission probabilities are also higher for intercalated dsDNA.

Figure 4

Schematic diagram of 8-bp dsDNA intercalated with ethidium intercalators at (a) two different sites, (b) at asymmetric positions of the dsDNA, i.e., at the second position and sixth position from the top. (c) The twist angle profile of asymmetrically intercalated and doubly intercalated dsDNA molecules. (d) Comparison of transmission probabilities of the bare dsDNA with intercalated dsDNA. (e) $V-I$ characteristics curve for dsDNA intercalated with different numbers of ethidium at different intercalation sites. (f) The DOS profile for the same systems as in (a) and (b).

Figure 5

Schematic diagram highlighting the base pairs of (a) bare dsDNA and (b) ethidium- and daunomycin-intercalated dsDNA. The top part of (b) represents the HOMO isosurface for the intercalated dsDNA part, with and without intercalator included in the calculation. The isosurfaces are similar, and the intercalator does not change the HOMO distribution significantly. (c) A comparison of the average transmission probabilities of the bare dsDNA and the intercalated dsDNA complexes in the region close to the Fermi energy. (d) The DOS for only the intercalated region. (e) Transmission probability curves in the region near the Fermi energy and (f) $V-I$ characteristic curves for the experimentally studied 8-bp dsDNA with sequence d-(GCTTGTTG) in the presence and absence of ethidium.

Figure 6

Transmission probability curve for the DNA and drug-DNA complexes (averaged over 50 morphologies) in the region close to the Fermi energy for 8-bp dsDNA sequence with and without intercalators for various electrode coupling values.

Figure 7

Transmission probability curve for the DNA and drug-DNA complexes (averaged over 50 morphologies) in the region close to the Fermi energy for 8-bp dsDNA sequence with and without intercalators for various asymmetric electrode coupling values. The left electrode coupling is kept fixed at ${\mathrm{\Gamma }}_l=0.1$ eV, while ${\mathrm{\Gamma }}_r$ is varied from 0.0001 to 10 eV. In all the cases, intercalated dsDNA has higher transmission than bare dsDNA.

Figure 8

Variation of current at 1 V vs Fermi energy averaged over 75 morphologies of bare dsDNA and dsDNA intercalated with ethidium and daunomycin. At any particular Fermi energy, intercalated dsDNA has higher current at 1 V relative to bare dsDNA.

Figure 9

HOMO level distribution on 8-bp (a) bare dsDNA and (b) dsDNA intercalated with ethidium, (c) dsDNA intercalated with daunomycin, and 12 bp (d) bare dsDNA and (e) dsDNA intercalated with ethidium, and (f) dsDNA intercalated with daunomycin.

Figure 10

Transmission probability curve for the DNA and drug-DNA complexes (averaged over 50 morphologies) in the region close to the Fermi energy for 8-bp dsDNA sequence with and without intercalators without backbone included in the calculations. This plot signifies the importance of backbone in charge transport in dsDNA.