Nitrogen doping of carbon nanoelectrodes for enhanced control of

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Nitrogen doping of carbon nanoelectrodes for enhanced control of DNA translocation dynamics Sang Won Jung, Han Seul Kim, Art E. Cho, and Yong-Hoon Kim ACS Appl. Mater. Interfaces, Just Accepted Manuscript • Publication Date (Web): 09 May 2018 Downloaded from http://pubs.acs.org on May 9, 2018

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ACS Applied Materials & Interfaces

Nitrogen doping of carbon nanoelectrodes for enhanced control of DNA translocation dynamics Sang Won Jung,1,† Han Seul Kim,2 Art E. Cho,1,* Yong-Hoon Kim2,* 1

Department of Bioinformatics, Korea University, Sejong, 2511 Sejong-ro Jochiwon-eup,

Sejong 30019, Korea 2

Graduate School of Energy, Environment, Water, and Sustainability, Korean Advanced

Institute of Science and Technology, 291 Deahak-ro, Yuseong-gu, Daejeon 34141, Korea †

Present address: Center for Supercomputing and Big Data, DGIST, 333 Techno jungang-

daero, Daegu 42988, Korea * Corresponding Authors: [email protected] and [email protected]

ABSTRACT Controlling the dynamics of DNA translocation is a central issue in the emerging nanoporebased DNA sequencing. To address the potential of heteroatom doping of carbon nanostructures to achieve this goal, herein we carry out atomistic molecular dynamics simulations for single-stranded DNAs translocating between two pristine or doped carbon nanotube (CNT) electrodes. Specifically, we consider the substitutional nitrogen doping of capped CNT (capCNT) electrodes and perform two types of molecular dynamics simulations for the entrapped and translocating single-stranded DNAs. We find that the substitutional nitrogen doping of capCNTs facilitates and stabilizes the edge-on nucleobase configurations rather than the original face-on ones and slows down the DNA translocation speed by establishing hydrogen bonds between the N dopant atoms and nucleobases. Due to the 1 ACS Paragon Plus Environment

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enhanced interactions between DNAs and N-doped capCNTs, the duration time of nucleobases within the nanogap was extended by up to ~ 300 %. Given the possibility to be combined with extrinsic light or gate voltage modulation methods, the current work demonstrates that the substitutional nitrogen doping is a promising direction for the control of DNA translocation dynamics through a nanopore or nanogap based of carbon nanomaterials.

KEYWORDS: DNA sequencing, capped carbon nanotubes, heteroatom doping, density functional theory calculations, molecular dynamics simulations

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1. Introduction Toward the goal of accomplishing an effective next-generation DNA sequencing scheme that will realize personalized or precision medicine, solid-state nanopores have emerged as a promising platform and significant research effort has been devoted into their development in the past few years.1-6 Compared with the more established bio-nanopores, solid state nanopores can allow the enhanced device stability and application of advanced fabrication technology available in semiconductor microelectronics industry. Their advantages also include the possibility to utilize readout methods other than longitudinal ionic currents and/or to more effectively incorporate novel low-dimensional nanomaterials such as graphene and carbon nanotubes (CNTs). For example, due to the atomically thin structure and unique electrical transport properties of graphene and CNTs, graphene nanopores,7-10 and grapheneor CNT-based nanogaps11-14 can possibly allow the detection of DNA sequence based on inplane transverse electrical currents and achieve the coveted single-molecule resolution.4-5 To realize the full potential of solid-state DNA sequencing based on novel lowdimensional nanomaterials and be able to read nucleobases at the molecular-level spatial resolution, in addition to the improved readout scheme, a high-fidelity control of DNA translocation dynamics still needs to be achieved.1,

3, 15-17

Specifically, one of the main

challenges is to reduce the speed of DNA translocation through a nanopore or nanogap. In the current technologies, the electrophoretic translocation speed of single-stranded DNA (ssDNA) is still too high (typically around 10 base/µs, being 103 − 104 times higher than that of biological pores) to correctly differentiate nucleobase at the single-base resolution.2 Moreover, if the molecular conformation within a nanopore/nanogap can be precisely controlled such that optimal nucleobase configurations for readout are induced and structural fluctuations are minimized, it should achieve the greatly increased sensing accuracy by 3 ACS Paragon Plus Environment


allowing the enhanced signal and minimized noise, respectively. While significant experimental advances have been made for the control of DNA translocation speed,18-24 they were mostly limited to the conventional nanopores made of inorganic materials such as SiN and the advance in the nanopores/nanogaps based on graphene and related two-dimensional materials have been rather insufficient.25-26 To make rapid progress in this field, as in the case for the conventional nanopore counterparts,16,

27-31

atomistic molecular dynamics (MD)

simulations are expected to become a valuable aid by providing various microscopic information and device design guidelines.12, 26, 32-37 For example, it was suggested that the reduction of the ssDNA translocation speed can be achieved by the hydrogenation of graphene edges,12 electrical biasing,34 or forming multilayer graphene layers.35 In this regard, a promising yet so far unexplored direction is the heteroatom doping, which is an important modification process of the sp2-bonded carbon network that has been proven to be beneficial for various potential device applications,38-39 and significant advances have been already made for their experimental realization.40 In this work, performing atomistic simulations, we study how the introduction of substitutional nitrogen dopant atoms into the sp2 carbon network affects the DNA translocation dynamics. As the carbon-based nano-constriction platform (Figures 1a and 1b), we employ CNT caps for which we have previously shown that the nitrogen doping significantly enhances the magnitude of tunneling currents as well as the chemical selectivity of different nucleobases.41 Regarding the choice of CNT cap geometry, we emphasize that the nanoscale curvature makes CNT and fullerenes distinctively different from other graphitic carbons in their ability to adsorb molecules.42-43 In this context, due to the resemblance between CNT caps and fullerenes, the results obtained here can be directly applied to the ssDNAs translocating on the fullerene-functionalized graphene44 or CNT sidewall45 or CNT 4 ACS Paragon Plus Environment

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tip46 (“nanobuds”). In terms of the device architecture, we envision that such one-dimensional nanogap can be embedded into a two-dimensional nanopore platform by, e.g., forming a buckypaper (Figure 1c).47 In view of the carbon curvature effect, another DNA sequencing platform where our study is relevant is the nanopores or nanoelectrodes based on graphitic polyhedral or folded graphene edges (Figure 1d),48 for which the slowing down of DNA translocation speed has been already demonstrated experimentally.25 Carrying out density functional theory (DFT) calculations for the capped CNT (capCNT) and N-doped capCNT (N-capCNT), we will first show that significant and nontrivial localized electronic modifications are induced from the substitutional N doping. Incorporating force-fields (FFs) calibrated to the DFT data, we then carry out equilibrium and non-equilibrium atomistic MD simulations for the ssDNAs entrapped and translocating between (N-)capCNTs, respectively. The comparisons between capCNT- and N-capCNTbased MD simulations demonstrate that the substitutional nitrogen doping facilitates the instant formation of hydrogen bonds between nucleobases and the N dopant atoms within NcapCNT electrodes, and results in the desired slowdown of DNA translocation speed and better-defined edge-on nucleobase configurations (aromatic rings of nucleobases are aligned along the CNT axial direction with their functional groups heading toward the CNT caps; see Figure 1b). Our work thus demonstrates that the heteroatom doping of carbon nanoelectrodes is a promising direction in view of controlling DNA conformations as well as reading nucleobases during ssDNA translocation processes.4, 41

2. Computational Methods 2.1 Models and FF MD simulations 5 ACS Paragon Plus Environment


FF MD simulations were performed using the NAMD program within the periodic boundary condition.49 CHARMM27 force field parameters were used for DNA,50-51 TIP3P water molecules,52 and ions.53 The parameters of carbon atoms for benzene in CHARMM27 force field were used for those of carbon atoms in capCNT.51, 54 The parameters for the carbon atoms bonded with the nitrogen atom in N-capCNT were those of type CG2R64, and the corresponding nitrogen atoms were those of type NG2R62, which were designed for 1,3,5triazine.55 Mulliken partial charges calculated with DFT were assigned to (N-)capCNT. Sodium (Na+) and chloride (Cl-) ions were added into the system as a concentration of 0.15 M. The final system measured 96 × 48 × 120 Å3 in size and included about 54,000 atoms. The MD integration time step used was 1 fs, and the particle-mesh Ewald scheme56 with grid density of 1/Å3 was employed for the descriptions of electrostatics. Van der Waals energies were calculated using a 12 Å cutoff. A Langevin thermostat was assumed to maintain constant temperature at 295 K. The CNTs were fixed during all the simulations. In all simulations, the prepared models were first energy minimized for 50,000 steps, followed by gradual heating from 0 to 295 K in 300 ps and equilibration for 1 ns, where the ssDNA was restrained and water molecules and ions were allowed to move. Production Set 1 simulations ran up to 10 ns with the phosphate (PO4−) group of ssDNA backbone being restrained. Repeating the simulation three times in each nucleobase case then produced multiple edge-on to face-on conformational changes and vice versa, and based on the total of 30,000 sampled configurations we analyzed the frequency of edge-on and face-on configurations in terms of the nucleobase rotation angle and its location within the nanogap (Figure 2a). For the Set 2 simulations, we performed two sets of simulations at 420 and 42 mV/Å of external electric fields EZ applied along the translocation direction z to drive the translocation of ssDNA. Production Set 2 MD simulations were run such that the entire 6 ACS Paragon Plus Environment

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translocation of nucleobases through the nanogap is captured (Figure 2b; see also Supporting Information Figure S1), and we observed that the translocation processes are completed in about 20 ps and 200 ps for the EZ = 420 and 42 mV/Å cases, respectively. More details on the Set 1 and Set 2 MD simulations will be presented in sections 3.2 and 3.3. Visualization and structure analysis were performed using the VMD software packagess .57 2.2 DFT Calculations To extract Mulliken charge distributions within (N-)capCNT electrodes, we carried out DFT calculations within the Perdew-Burke-Ernzerhof parameterization of generalized gradient approximation58 using the SIESTA software.59 Troullier-Martins-type norm-conserving pseudopotentials are employed to remove the core electrons.60 The Kohn-Sham orbitals were expanded in terms of the double-ζ-plus-polarization level numerical atomic basis sets constructed with the confinement energy of 80 meV. The exchange-correlational energy and Hartree potential were calculated with a mesh cut-oﬀ energy of 300 Ry. CNT caps were introduced at the end of six unit cell-long (5,5) CNT. A sufficiently large vacuum region of 15 Å was included to avoid artificial interactions with neighboring images, and only the gamma point was sampled for Brillouin zone integration.

3. Results and discussion 3.1 Electron distribution within pristine and N-doped CNT caps As the nano-constriction platform, we employed capped (5,5) CNTs with the diameter of 6.8 Å (Figure 3a), which is shorter than the spacing of ~ 7 Å between adjacent nucleobases in a stretched ssDNA.41 N-capCNTs were prepared by substituting a carbon atom among the 5membered-ring at the tip of capCNT with an N dopant atom (Figure 3b). To address the 7 ACS Paragon Plus Environment


effects of a substitutional N atom on the spatial charge distributions within the CNT cap, we compared the Mulliken charge populations of N-capCNT with those of capCNT. Recent experimental studies have shown that the nature of N-doped graphene can be rather complicated due to the diverse atomic bonding possibilities,61 and we recently demonstrated that the Mulliken charge visualization is a powerful tool to develop the atomistic understanding of the bonding nature of N atoms embedded in an sp2 carbon network.62 A key finding from these studies was that there arise significant local charge fluctuations near the substitutional N atoms before a rather uniform net electron doping is achieved in the longrange region (beyond ~ 7 Å radius). For the N-doped graphene, we found the Mulliken population of − 0.402 e per nitrogen atom,62 which is in good agreement with the experimentally estimated value of −0.42 e.61 We will now show that overall similar N-induced charge transfer characters are developed even within the curved geometry of CNT caps. First, considering the pristine CNT cap case, we observe that the presence of curvature accompanying a five-membered ring already induces finite spatial charge distributions but their magnitudes are very small (Figure 3a): While each atom at the first five-membered carbon ring equally donates electrons by − 0.001 e, other atoms within the cap accept electrons by around +0.004 ~ 0.005 e each. The net induced charge within the cap region was +0.115 e, and this is compensated by the tube region connected to the cap. On the other hand, in the N-capCNT case, we find that the magnitudes of charge distributions between the substitutional N and surrounding C atoms are several orders of magnitude larger (Figure 3b): The net Mulliken charge of the substitutional N dopant is −0.349 e, and most of these charges are transferred to the carbon atoms bonded to N, which results in the excess charge of +0.071 e for C1 and C2 located within the pentagon ring and the larger amount of +0.105 e for C3. The net charge within the cap 8 ACS Paragon Plus Environment

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region was −0.065 e for the N-capCNT and again this is compensated by that of the tube region connected to the cap. We emphasize again that such strong electron donating nature of the substitutional N dopant is consistent with that found in the substitutional N-doped graphene.61-62 Having observed that the introduction of a substitutional N atom within graphene or CNT caps induces a strongly localized charges, one could expect that they can experience drastically different and possibly enhanced electrostatic interactions with ssDNA compared with their undoped counterparts.

3.2 Conformational dynamics of ssDNA between N-doped CNT caps We now move on to the FF MD simulation results, and discuss how the substitutional N doping of CNT cap affects the conformation of nearby ssDNAs and particularly their translocation dynamics. To prepare junction models, two capCNTs or N-capCNTs were mirror-symmetrically placed with a gap distance of 12.0 Å which is large enough for the nucleobases to pass through in the edge-on configurations. Moreover, to systematically address the problem, we performed two sets of FF MD simulations using a ssDNA model composed of 5’-A1-G2-C3-T4-A5-G6-C7-T8-3’ (where A, G, C, T respectively stands for adenine, guanine, cytosine, and thymine) with the central four nucleobases C3-T4-A5-G6 utilized for analysis (see Supporting Information Figure S1): (1) First, we carried out equilibrium MD simulations for the nucleobases placed at the nanogap midpoint and observed the impact of substitutional N dopant atoms on the occurrence of edge-on nucleobase conformations (Set 1; see Figure 2a). (2) Next, by applying the electric fields EZ of 420 mV/Å and 42 mV/Å along the translocation z direction, we performed nonequilibrium steering MD simulations and studied the actual DNA translocation dynamics (Set 2; see Figure 2b). To ensure the reliability of conclusions, we repeated the calculation three 9 ACS Paragon Plus Environment


times for each simulation set. Note that the distance of ~ 7 Å between the DNA backbone and the nanogap midpoint is large enough for the backbone PO4- groups neutralized by solvent Na+ ions not to prevent the approach of nucleobases toward the N doping sites within the NcapCNT tips. We first discuss the results from the equilibrium Set 1 simulations. Here, to describe the orientations of nucleobases, a set of basis vectors was defined as follows (Figure 1b and Figure 4 left panels):

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We first defined a unit vector e1 pointing from C4 to N1 atoms in

purines (adenine and guanine) and from C6 to N3 in pyrimidines (cytosine and thymine). To determine e2, we then defined a vector e2* pointing from C4 to C6 in purines and from C6 to C4 in pyrimidines. The vector e2 was then set as the unit vector proportional to e2* − (e2* · e1) e1. The unit vector e3 was finally defined as e3 ≡ e1 × e2. To describe these orientations more succinctly, we will use the angle θ, which was defined as the angle between the vector e3 and the direction z normal to the CNT axis (Figures 1b and 4). Note that the θ angle quantifies the preference of edge-on conformations of nucleobases, where |θ| = 0 ° and |θ| = 90 ° correspond to the ideal edge-on and face-on modes, respectively. In addition to the nucleobase rotation angle, we used the distance of the nucleobase center of mass from the nanogap middle point d to identify the face-on or edge-on conformations. Then, we assigned the nucleobase conformation that meets the criteria |θ| ≤ 30 ° and | d | ≤ 2 Å (|θ| ≥ 60 ° and | d | > 2 Å) as the edge-on (face-on) configuration (Figure 2a). Note that we do not assign the configurations with |θ| ≥ 60 ° and | d | ≤ 2 Å as the face-on mode because of the long distance between the nucleobase and (N-)capCNT electrode (> 4 Å) or the minimal interaction between them. In Figure 4 right panels and Table I, we summarize the Set 1 equilibrium MD simulation results (see Supporting Information Figure S2 for more detailed analysis). Note that overall the constraint of fixed PO4− group in Set 1 MD simulations prevents a significant 10 ACS Paragon Plus Environment

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proportion from adopting either the face-on or edge-on conformation. First, for the capCNTbased junction cases, we observe that nucleobases dominantly adopt the face-on conformation with the only exception of dCMP. The trend can be understood in terms of the driving force to maximize π-π interactions between a CNT cap and the aromatic ring of nucleobases.63 The face-on conformation frequency of deoxyadenosine 5′-monophosphate

(dAMP), deoxyguanosine 5′- monophosphate (dGMP), deoxycytidine 5′-monophosphate

(dCMP), and deoxythymidine 5′-monophosphate (dTMP) were 15.3 %, 15.9 %, 0.2 %, and 12.7 %, respectively, or the tendency ordering for the face-on conformations was dGMP ≳ dAMP > dTMP > dCMP. The negligible face-on frequency of dCMP implies that its interaction with capCNT is not strong enough to overcome the above-mentioned constraint of fixed backbone. Overall, it is natural for purines with 9-membered double rings (dAMP and dGMP) interact more strongly to graphitic systems than pyrimidines with 5-membered rings (dTMP and dCMP). Indeed, for the nucleobases adsorbed on carbon-based systems such as C60, single-wall carbon nanotubes, graphene, and graphite surface, the face-on tendency ordering of dGMP > dAMP > dTMP > dCMP was typically observed or calculated.64-67 On the other hand, we find that N-capCNTs induce significantly enhanced edge-on conformations for all four nucleobases: The edge-on conformation frequencies of dAMP, dGMP, dCMP, and dTMP were 18.9 %, 30.3 %, 11.0 %, and 15.6 %, respectively, giving the preference ordering of dGMP > dAMP > dTMP > dCMP for the edge-on conformation. Observing the time-dependent nucleobase conformations, we find that the “lifetime” of edgeon nucleobase conformations, or the edge-on to face-on conformational conversion time, also follows the same order (Supporting Information Figure S3). We also note that, in addition to the individual edge-on conformational frequency, the combined face-on and edge-on 11 ACS Paragon Plus Environment


conformational frequency increases from ~ 10 – 20 % in the capCNT case to ~ 16 – 32 % range in the N-capCNT case, indicating the overall enhanced interactions between nucleobases and N-doped CNT electrodes. Regarding the atomistic origins of the observed conformational changes, we interpret that the π-π interactions, which were dominant for the pristine capCNT case, are now interrupted by hydrogen boding interactions between the substitutional N atoms within CNT caps and the functional groups in nucleobases. Specifically, we observed that the bonds involving -C2-H and –C8-H in dAMP, -C2-N2-H2 and –C8-H in dGMP, -C4-N4-H2 and -C5H in dCMP, and –N3-H, -C5-CH3, and -C6-H in dTMP are established (see Supporting Information Figure S4). Particularly, the maximization of edge-on conformations in the dGMP case can be understood by the fact that two functional groups, -N1-H and -C2-N2-H2 on one side of guanine and -C8-H on the opposite side establish hydrogen bonds with the substitutional N dopant atoms on the two N-capCNTs in a linear geometry. Of course, its large molecular size should also help to establish stronger attractive interactions with NcapCNTs.

3.3 Electric field-driven translocation of ssDNA through N-doped CNT caps Having identified in Set 1 simulations the clear potential advantage of the substitutional N doping of capCNTs in controlling the nucleobase conformations (by effectively increasing the lifetime of edge-on nucleobase conformations, or the preference for edge-on modes), we now discuss the Set 2 steering MD simulations that allow us to observe the realistic translocation dynamics in the existence of electrophoretic electric field (Figure 5; see also Supporting Information Figure S5 and Movies S1-S8). Here, initial molecular geometries 12 ACS Paragon Plus Environment

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were prepared by displacing the C3, T4, A5, and G6 conformations between the N-capCNT electrodes obtained in Set 1 simulations by +5.0 Å along the z direction and additionally aligning them to assume nearly edge-on configurations (θ ~ 0 °; see Supporting Information Figure S1). As the translocation simulation progresses, we focused on the main observables that include the time until each nucleobase enters into the nanogap (τentry), its dwell time within the nanogap (τdwell), and the nucleobase configurations (i.e. the edge-on vs face-on conformation). Overall, we observed in the Set 2 simulations stepwise or ratcheting translocations, which was often observed in the graphene nanopore platform.26, 34, 36-37 Before discussing the details, we emphasize that the conclusions from EZ = 420 mV/Å and EZ = 42 mV/Å Set 2 simulations are qualitatively similar, ensuring the validity of the conclusions presented below. Considering first the capCNT-based junctions, we note that, irrespective of the initial geometries, the external electric field exerted along the translocation z direction resulted in the dominantly face-on configurations (θ ~ 90 °) within the nanogap (indicated by red shaded area). This tendency is driven by the π-π attractions between nucleobase and CNT caps discussed in Sec. 3.2 regarding Set 1 simulations. Additionally, it should have been further strengthened by the additional interactions between the electrophoretic external electric field and net dipole moment of nucleobases (experimentally measured as 2.5, 7.1, 7.0, 4.1 Debye for A, G, C, and T, respectively).1 In terms of the latter coupling between the nucleobase dipole moments and the electric field along the translocation direction, we point out that the face-on conformations should be common to all the nanopore sequencing platforms that involve electrophoretic DNA translocations. Here, while all the nucleobases eventually assume the face-on configurations before entering into the nanogap, we could observe that the size of nucleobases affect the speed of conformational change: Whereas the pyrimidine13 ACS Paragon Plus Environment


based dCMP and dTMP are abruptly rotated from the edge-on to face-on modes within only about ~ 2 ps at EZ = 420 mV/Å (~ 10 ps at EZ = 42 mV/Å), purine-based dAMP and dGMP are gradually aligned along the z direction for ~ 10 ps at EZ = 420 mV/Å (~ 80 ps in EZ = 42 mV/Å). Moreover, we note that the nanogap entrance time τentry is also affected by the size of nucelobases and on the average the larger purines (dAMP and dGMP) enter into the nanogap faster than the smaller pyrimidine counterparts (dCMP and dTMP). This behavior can be again understood in terms of the dominance of π-π interactions between nucleobases and CNT caps, which should be bigger for the larger purine group. Focusing now on the N-capCNT electrode case, we observe that it provides several advantages in terms of the translocation dynamics. Most notably, we observe that the nucleobases now enter the nanogap much faster than in the capCNT case and they now adopt the edge-on conformations rather than the face-on one. Both of these features reflect the H bonding-induced attractive forces between the functional groups of nucleobases and N-doped CNT caps discussed in Sec. 3.2. Accordingly, the trend for purine groups to enter into the gap faster than pyrimidine groups observed above for the capCNT case now disappeared. For example, when the electric field EZ = 420 mV/Å (EZ = 4 mV/Å) is applied, the entry time of dGMP into the N-capCNT nanogap was τentry = 0.3 ps (7 ps) while it was τentry = 5.7 ps (20 ps) for the capCNT nanogap case. These features were consistently observed in other MD sets (see Supporting Information Figure S5). Next, in terms of the retention time within the nanogap τdwell (indicated by blue shaded area), we observe that it has been significantly increased compared with that for the capCNT case. The increase in the retention time reached up to 295 % and 254% for the EZ = 420 mV/Å and EZ = 42 mV/Å cases, respectively. In terms of nucleobase conformations, as in the entry behavior and can be also expected from the Set 1 simulations, they are now much closer to the edge-on mode. Note that here we did 14 ACS Paragon Plus Environment

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not include the effects of electric field along the CNT axial direction resulting from the bias voltage that can be applied to read the nucleobases based on transverse electrical currents. 20, 24

Molecular dipole interactions with the electric field across nanogap was recently shown to

restrict the configurational degrees of freedom of even molecules with smaller dipole moments than nucleobases (benzenediamines),68 and we expect that its inclusion will further enhance the edge-on configurations of nucleobases and concurrently increase the retention time.

4. Conclusions In summary, carrying out combined DFT-FF multiscale simulations, we demonstrated that the substitutional N doping of sp2 carbon network significantly improves the controllability of DNA translocation dynamics, a critical element for the next-generation DNA sequencing. First, to prepare the FF simulation protocols, we carried out DFT calculations to identify the charge redistribution within CNT cap induced by the nitrogen doping. Then, we carried out equilibrium FF MD simulations and showed that the N doping of capCNTs can enhance edge-on configurations (rather than typical face-on conformations) of nucleobases via the N dopant atoms-inducedhydrogen bonding interactions. Performing non-equilibrium steering MD simulations, we finally studied the actual electrophoretic ssDNA translocations through the nanogap between capCNT nanoelectrodes. For the case of pristine capCNT electrodes, we found that the translocation speed and conformations of ssDNA are dominated by the π-π interactions between nucloebases and CNT caps and the interaction between nucleobase dipole moments and external electric field. However, upon the N doping of capCNT electrodes, we found that the additional hydrogen bonding and electrostatic attractions accelerate the entrance of nuclobases into the nanogap, increase the retention time of 15 ACS Paragon Plus Environment


nucleobases within the nanogap, and induce dominantly edge-on conformations of nucleobases. Specifically, we found that the N doping of capCNTs reduces the translocation speed by up to ~ 300 %. Our work thus demonstrates that the substitutional heteroatom doping of carbon nanoelectrode provides an attractive route toward the enhanced controllability of DNA translocation dynamics. In closing, we emphasize that the intrinsic modification scheme proposed here can be straightforwardly combined with the extrinsic methods such as light21 and/or gate voltage20, 24, 68 modulation to achieve better alignment and increase the nanopore/nanogap dwell time for the translocating DNA.


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ASSOCIATED CONTENT Supporting Information Additional data from the Set 1 equilibrium and Set 2 steering MD simulations. The time evolution of the absolute value of angle θ starting from the edge-on conformation in Set 1 simulations, the time evolution of the absolute value of angle θ starting from the face-on conformation in the capCNT Set 1 simulations, the dominant H-bonding interaction configurations of nucleobases between N-capCNTs, and the additional sets of time propagation of angle θ in Set 2 simulations Videos of Set 2 non-equilibrium steering MD simulations for the EZ = 420 mV/Å (Supporting Information Movies S1—S4) and EZ = 42 mV/Å (Supporting Information Movies S5—S8) cases.

Acknowledgements This work has been supported by the Nano-Material Technology Development Program (Nos. 2016M3A7B4024133, 2016M3A7B4025405, and 2016M3A7B4909944) of the National Research Foundation (NRF) funded by the Ministry of Science and ICT of Korea. H.S.K. and Y.-H.K. were additionally supported by the NRF Basic Research Program (No. 2017R1A2B3009872), Global Frontier Program (No. 2013M3A6B1078881), Basic Research Lab Program (No. 2016M3A7B4909944), and Pioneer Program (2016M3C1A3906149). S.W.J. and A.E.C. were additionally supported by NRF Grant No. 2017R1D1A1B03035870. Computing resources have been provided by the DGIST supercomputing and big-data center.



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TABLES Table 1. Frequency analysis of the four nucleobase conformations from the Set 1 MD simulations (three separate simulations with the total of 30,000 sampled conformations in each nucleobase case). Face-on and edge-on configurations were determined according to the criteria shown in Figures 2a and 4. See also Supporting Information Figure S2. capCNT face-on

edge-on

N-capCNT others

face-on

edge-on

others

dAMP

15.3 %

3.7 %

81.0 %

13.1 %

18.9 %

68.0 %

dGMP

15.9 %

4.4 %

79.7 %

1.1 %

30.3 %

68.6 %

dCMP

0.2 %

9.6 %

90.2 %

5.2 %

11.0 %

83.8 %

dTMP

12.7 %

2.5 %

84.8 %

9.8 %

15.6 %

74.6 %


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FIGURES

Figure 1. (a) A schematic of a CNT electrodes-based DNA sequencing device, where a stretched ssDNA segment (5’-A1-G2-C3-T4-A5-G6-C7-T8-3’) is located between the (N)capCNT electrodes. Water molecules and Na+ and Cl- ions are omitted for clarity. (b) Definition of the angles θ introduced to characterize the orientation of each nucleobase in Set 1 and Set 2 simulations. It is defined as the angle between the vectors e3 and z, where z is the translocation direction and perpendicular to the cylindrical axis of (N-)capped CNTs. Schematics of DNA sequencers based on (c) a buckypaper nanopore that encloses a CNT electrode with a nanogap formed at the nanopore and (d) graphitic polyhedral (folded graphene) edges.



Figure 2. (a) Schematics of the Set 1 equilibrium MD simulations. For each nucleobase placed at the midpoint of the (N-)capCNT electrodes, we extracted its tendency to form faceon or edge-on configurations (red- and blue-shaded regions, respectively) based on the angle θ (Figure 1b) and the nucleobase center of mass location with respect to the nanogap midpoint (see text as well as Figure 4 for details). (b) Schematics of the Set 2 non-equilibrium steering MD simulations. By applying an external electric field z to drive a single-stranded DNA model (Figure 1a), we extracted the entry time τentry into the nanogap region (indicated by the black dashed lines) as well as the dwell time τdwell within the nanogap.


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Figure 3. Charge distributions within the pristine and N-doped capped CNTs. Real-space projections of Mulliken populations are shown for the top (top panels) and side views (bottom panels) of (a) capCNT and (b) N-capCNT. Electron loss and gain are represented as blue and red colors, respectively. The green circle in the top panel of (a) indicates the first five-membered carbon ring located at the tip.



Figure 4. Definition of basis vectors used to specify the nucleobase orientation (left panels), and the nucleobase conformational distributions from the capCNT-based (middle panels) and 26 ACS Paragon Plus Environment

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N-capCNT-based (right panels) Set 1 MD simulations (three simulations with 30,000 total sampling points each) for the (a) dAMP, (b) dGMP, (c) dCMP, and (d) dTMP cases. On the middle and right panels, the criteria used to assign face-on and edge-on configurations (see text as well as Figure 2a for details) are indicated as red- and blue-shaded regions, respectively. Shown together are the histograms for the normalized frequency of nucleobase conformations that meet either the face-on or edge-on angle (right panels) and distance conditions (upper panels).



Figure 5. Time propagations of the absolute value of angle θ in the Set 2 simulations for the (a) dAMP, (b) dGMP, (c) dCMP, and (d) dTMP cases. The external electric fields of EZ = 420 mV/Å (left panels) and EZ = 42 mV/Å (right panels) were applied to translocate each 28 ACS Paragon Plus Environment

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nucleobase into the nanogap. The dwell times (τdwell) within the nanogap region are indicated as red- and blue-shaded boxes for the capCNT and N-capCNT cases, respectively. Histograms of |θ| taken during τdwell are shown together on the right hand side.



Table of Contents Figure


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Nitrogen doping of carbon nanoelectrodes for enhanced control of

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