Simulative Analysis of a Truncated Octahedral DNA Nanocage Family

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Simulative Analysis of a Truncated Octahedral DNA Nanocage Family Indicates the Single-Stranded Thymidine Linkers as the Major Player for the Conformational Variability Francesco Oteri,† Mattia Falconi,† Giovanni Chillemi,‡ Felicie F. Andersen,§ Cristiano L.P. Oliveira,||,# Jan S. Pedersen,|| Birgitta R. Knudsen,§ and Alessandro Desideri*,†,^ †

)

Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy; CIBB, Center of Biostatistics and Bioinformatics, Via della Ricerca Scientifica, 00133 Rome, Italy; and Interuniversity Consortium, National Institute Biostructure and Biosystem (INBB), Rome, Italy ‡ CASPUR Interuniversity Consortium for the Application of Super-Computing for Universities and Research, Via dei Tizii 6, Rome 00185, Italy § Department of Molecular Biology and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, C.F. Møllers Alle, Bldg. 130, 8000 Aarhus C, Denmark Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark ^ NAST Nanoscience & Nanotechnology & Innovative Instrumentation, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133 Rome, Italy

bS Supporting Information ABSTRACT: Three nanocages composed of 12 DNA double helices, linked by single strand thymidine linkers made by 3, 5, and 7 nucleotides, have been characterized through classical molecular dynamics simulation to evaluate in silico the specific structural and conformational features generated by the use of a thymidine bridge of different length. The three simulated nanocages are stable, and their dynamics is characterized by a slight rotational motion of the double helices, induced by the conformational variations of the thymidine linkers. Despite this rotation the helices maintain a B-DNA structure as indicated by the values of their geometrical parameters. The thymidine strands are the elements having the largest displacement from the initial 3D model and give a significant contribution to the organization of the scaffold geometry throughout definite arrangements of base stacking and hydrogen bonds between the bases. Comparative analysis indicates that the linker length modulates the interactions occurring between the thymidines conferring a conformational variability larger in the 5T and 7T than in the 3T cage.

’ INTRODUCTION During recent years the number of presented two- (2D) or three-dimensional (3D) DNA nanostructures has exploded. The field of DNA nanoscience was initiated in the early 1990s by Seeman, who presented the design and construction of a DNA nanostructure with the connectivity of a cube.1 Since then, a tremendous amount of DNA nanostructures including 2D origamis,25 tiles,6,7 3D polyhedral813 origami-based honeycomb or box shapes,14,15 and crystals16 have been published. The success in constructing these structures is based on the selfassembly property of the specific G-C or A-T DNA base pairs. Consequently, successful assembly relies on the design of DNA sequences that not only allow formation of the intended product based on complementarity between the base sequences of the utilized DNA strand but also limit assembly of other products competitive to the target. The final products are macroscopic objects having nanometric dimensions that can be investigated r 2011 American Chemical Society

by advanced spectroscopic techniques such as small angle X-ray scattering (SAXS), cryo-electron microscopy (cryo-TEM), and atomic force microscopy (AFM), which are all techniques able to provide many structural details although they cannot reach a structural description at the atomistic level. The most powerful approach to describe the correlation between the atomistic and the macroscopic 3D structure of a molecule is to obtain an X-ray diffraction image at high resolution of the molecule in a crystal form. A beautiful example of this is provided by Seeman and coworkers, who provided the link between atomic and molecular scale by presenting the crystal structure at 4 Å resolution of a selfassembled 3D crystal based on the DNA tensegrity triangle.16 However, DNA nanostructures are often difficult and/or Received: April 29, 2011 Revised: July 28, 2011 Published: July 29, 2011 16819

dx.doi.org/10.1021/jp203999x | J. Phys. Chem. C 2011, 115, 16819–16827

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Figure 2. Time evolution of the DNA nanocage rmsd from the starting structure for the 3T (A), 5T (B), and 7T (C) nanocages. The black, red, and green curves represent the values calculated for all of the atoms, the DNA double helices, and the thymidine strands, respectively. The gray box indicates the trajectory fraction not considered for the analysis. Figure 1. Spacefill representations of the starting DNA nanocage structures. The nucleotides are colored by atom type. (A) 3T nanocage, (B) 5T nanocage, and (C) 7T nanocage. The picture was generated using the PyMol program.38

expensive to crystallize, which is why classical molecular dynamics (MD) simulations, carried out on a starting model built from the constraints given by the experimental data, offers an attractive alternative, and in some cases the only possible, approach to obtain a detailed description of the atomistic interactions. MD simulations have been used to describe the structure and stability of various paranemic crossover DNA molecules,17 and more recently a 12 ns long simulation has been used to investigate the properties of a truncated DNA octahedral nanocage structure composed of 12 double helices, each one connected by single stranded linkers made by seven thymidines (cage 7T).18 Experiments on the assembly of nanocages based on the above-mentioned structural framework having the 7T linker regions replaced with linker regions with lengths ranging from 2T to 6T demonstrated that 3T linker regions constitute the minimum linker length that supports efficient cage assembly. The inability of cage 2T to assemble has been explained by the high degree of deformation of the hydrogen bonds between the bases at the extremities of the double helices in this structure.19 In this work three representative members of the nanocage family, namely nanocages 3T, 5T, and 7T (Figure 1AC), have

been characterized through extensive MD simulation (50 ns) to evidence the relationship between the linker length and the cage stability and flexibility. The simulations indicate that the variability of the hydrogen bonds and stacking interactions, occurring between the thymidines within the linker, generates a rotational motion of the double helices which is slightly higher both in cages 5T and 7T than in cage 3T.

’ METHODOLOGY Starting Model Building. The 3T, 5T, and 7T nanocage models (Figure 1AC) were built using a homemade program that works in two stages. Initially the structure of the 12 helices, forming the cages, prebuilt through the 3DNA program20 have been assembled to obtain an ideal truncated octahedral geometry having a radii of 50, 56, and 63 Å for the 3T, 5T, and 7T cages, respectively, corresponding to the dimensions of the cages, experimentally obtained from SAXS experiments.19 The optimal helices orientation and relative distances have been obtained in the absence of the single-stranded thymidine linkers, imposing as geometrical constraint the invariance of the octahedron radius and finding the minimum value for S that is defined as it follows:

S¼ 16820

24

∑ ðDi Þ2 i¼1

ð1Þ

dx.doi.org/10.1021/jp203999x |J. Phys. Chem. C 2011, 115, 16819–16827


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Figure 3. Per nucleotide local RMSF for each of the two strands of the 12 DNA double helices for the 3T, 5T, and 7T nanocages. The star and the circle refer to nucleotides belonging to the complementary strands of the double helix. The red, green, and blue colors refer to the 3T, 5T, and 7T cages, respectively.

where i is the thymidine linker index and Di is the length of the thymidine linker. The preliminary geometrical minimization aimed at defining the helices positions was carried out using the Powell algorithm 21 embedded in the python scipy module (http://www.scipy.org). Once the optimal DNA helices orientations have been reached, the thymidine linkers have been manually added using the program SYBYL 6.0 (TRIPOS, http://www.tripos.com/) and the clashes removed through the SYBYL anneal module. The topology, i.e., the file containing all of the data required to simulate the molecules, of the nanocages has been obtained through the tleap AMBER9 suite program module22 and the cages have been parametrized through the AMBER99 force-field,23 with the parmbsc0 corrections.24 The MD simulated structures have been immersed in a truncated octahedral water box, using TIP3P water molecules,25 neutralizing the system charges with 504, 552, and 600 Na+ counterions for 3T, 5T, and 7T nanocages, respectively, placed in electrostatically preferred positions, imposing a minimal distance between the solute and the box walls of 14 Å. Equilibration Protocol and MD Simulations. Three minimizations have been carried out before running the simulations: the first, in which restraints of 500 kcal/mol have been imposed on all of the nanocage atoms to minimize the water and the ions; the second, in which restraints of 500 kcal/mol have been imposed on the double helices only, to minimize the thymidine linkers and the third, executed without imposing restraints, to minimize the entire system. The MD simulations of the 3T, 5T, and 7T cages have been carried out using NAMD 2.726 program. Three MD runs, each 200 ps long, at 100, 200, and 300 K have been carried out to equilibrate the structures. The systems have been simulated in periodic boundary conditions, using a cutoff of 10 Å for the

evaluation of short-range nonbonded interactions and the PME method for the long-range electrostatic interactions.27,28 The SHAKE29 and SETTLE30 algorithms were used to constrain all bond lengths, for the nucleic acid and water, respectively. The temperature has been fixed at 300 K using the Langevin dynamics, whereas pressure has been held constant at 1 atm through the Langevin piston method.31,32 The three nanocage models have been simulated for 50 ns and the atomic positions saved every 250 steps (i.e., 0.5 ps) for the analyses. The systems have been simulated using 72 cores on the MATRIX cluster at CASPUR calculation center composed by 318 nodes, each with two AMD Opteron quadcore CPUs, for a total of 2512 cores. Analysis. Root mean square deviations (RMSDs), root mean square fluctuation (RMSFs), and radii of gyration of the trajectories have been calculated by using the GROMACS 4.033 analysis tools. The first 15 ns have been removed and the remaining trajectories have been used for the analyses. The RMSF has been calculated using two different approaches. The first one called local RMSF has been calculated for each of the twelve double helices extracted from the total cage and singly fitting each of them without taking into account the total cage motion. The second one called global RMSF has been calculated fitting the total cage conformation. In this last case the RMSF values are influenced by the total cage motion. In both cases the RMSF values have been calculated over the phosphor atoms. The DNA curvature and the geometrical parameters have been calculated using the program CURVES.34 A stacking between the linker bases has been considered to occur if the basebase distance (i.e., the distance between the geometric centers of the bases) is lower than 5 Å and the base base plane angle reaches a value between 0 and 30 (cis-stacking) or between 150 and 180 (trans-stacking). 16821



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Figure 4. Per nucleotide global RMSF, for each of the two strands of the DNA double helices of the 3T (A), 5T (B), and 7T (C) nanocages. The star and the circle refer to the nucleotides belonging to the complementary two strands of the double helix. (D) Schematic representation of the relation between global RMSF and double helix rotation. The black line represents the rotation axis, the RMSF values increase from the blue to the red colors. The helix representation has been obtained using the program QuteMol.39

The free energy difference, related to the equilibrium in each linker between the conformations containing or not containing stacked bases, has been calculated using the following formula: Nbs ΔGS ¼ RTln ð1Þ Nbns where Nbs indicates the number of frames where at least two bases are stacked while Nbns is the number of frames where not stacked bases have been detected. A T-shaped conformation35,36 between two bases in a linker has been considered to occur if the basebase distance (i.e., the distance between the geometric centers of the bases) is lower than 7 Å and the basebase plane angle reaches a value between 85 and 95 or between 265 and 275. The ΔG value, characterizing the equilibrium in each linker between conformations containing or not containing T-shaped bases, has been evaluated using the following formula: Nt ð2Þ ΔGT ¼ RTln No where Nt represents the number of frames in T-shaped conformations35,36 and No indicates the number of frames for all the other conformations. The hydrogen bond analysis has been performed through g_hbond GROMACS module, in house modified to print a list of the hydrogen bonds detected for each frame. The hydrogen bonds have been defined as interlinker hydrogen bonds when

established between two bases located on two different linkers, or as intralinker when established between bases belonging to the same linker.

’ RESULTS AND DISCUSSION Root Mean Square Deviations and Gyration Radius. Figure 2 shows the rmsd calculated over the full trajectories, for cages 3T, 5T, and 7T, considering the entire cage (black line), the double helices only (red line), or the thymidine linkers only (green line). The three RMSDs reach stability after the first 5 ns, but to be sure that the analyzed trajectories are well thermalized, all of the analysis have been carried out over the last 35 ns, removing the first 15 ns. The figure shows that the thymidine linkers have a deviation greater than the helices, indicating that they are the elements undergoing the greatest conformational changes from the initial structure. The rmsd evaluated using as a reference the average structure indicates that the 3T nanocage shows a reduced conformational sampling in comparison with the 5T and 7T ones (Figure S1 of the Supporting Information). Overall, all three cages are quite stable as confirmed by the time evolution of the linker gyration radius (Figure S2 of Supporting Information) which starts from a value of 61, 68, and 74 Å for cages 3T, 5T, and 7T, respectively, and reaches average values of 55, 61, and 65 Å, in good agreement with the experimental radius of the nanocages.19 Double Helices Local and Global Root Mean Square Fluctuations. The local and global RMSF of the nucleotides composing the 12 DNA double helices of each cage are reported 16822



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Figure 5. (A) Upper half shows a schematic nanocage where the six square faces (from I to VI), having the thymidines strands as sides, and the 12 double helices (from DH1 to DH12) are evidenced. In the lower side of the figure an atomistic 7T nanocage, with the same orientation of the schematic picture, is represented. (BD) schematic representations over the molecular contour of the six square faces belonging to the 3T, 5T, and 7T nanocages, respectively. The red filled squares represent the bases and the hydrogen bonds are indicated by colored dashed lines with a frequency corresponding to the colored scale. The bases having a stacking interaction present more than 70% of the simulation time are enclosed by circles connected by blue lines. The spacefill representations have been obtained using the program PyMol38 and QuteMol.39

for cages 3T, 5T, and 7T in Figure 3 and 4, respectively. For all three cages the local RMSF (Figure 3), calculated separately for each helix, shows a symmetric trend for the two DNA strands, as usually found in any simulated double helix,37 with the internal nucleotides characterized by an average RMSF of about 2 Å and the tail nucleotides by larger values. The global RMSF for each cage (Figure 4AC), calculated by fitting each total cage,

displays a more complex behavior that contains information on the cage global motion. The RMSF of the helices have a sinusoidal trend, more marked in the 5T and 7T cage double helices (Figure 4, panels B and C), indicating a rotational motion that roughly occurs around an axis tangential to the external border of the helix (Figure 4D). The axis is not always parallel to the main double helix central axis but is in some cases either 16823



Figure 6. (A) Detail of interlinker hydrogen bonds established between two thymidines (dashed lines) located at the extremity of two different linkers. The thymidines are also stacked (dotted gray ellipsoids) with the last base pair of the double helix strands from which they branch. (B) Detail of a 3T linker in which the thymidines are not involved in interactions. (C) Detail of a 7T linker in which the thymidines are involved in several stackings. The picture has been obtained using the program Chimera.40

shifted or with a different inclination. The sinusoidal trend, shown by the majority of the helix strands, with the nucleotides close to the axis characterized by low fluctuation values and the nucleotides far from the axis characterized by large fluctuation values (Figure 4D), indicates that one of the main components of the global motion of the cages 5T and 7T is characterized by a rotational motion of the double helices. Double Helices Geometrical Parameters. All of the geometrical parameters characterizing the standard B-DNA helix have been monitored and averaged along the trajectory to accurately analyze each possible geometrical deformation of the 12 DNA double helices of each cage. The average values, with their standard deviations, are shown in Tables 13 of the Supporting Information, together with the standard B-DNA geometrical parameters for comparison. The average calculated parameters are close to the typical B-DNA geometrical values indicating a good stability and a regular geometry of the double helices, which are maintained during the entire simulation time. The rmsd from an ideal B-DNA helix, calculated as a function of time for each double helix and for each nanocage (Figure S3 of Supporting Information), shows an almost constant displacement of about 5.0 Å that, together with the stability of all the B-DNA geometrical parameters (Tables S1 and S2 of the Supporting Information), with exception of the curvature (Table S3 of the Supporting Information), indicates that the helices maintain a B-DNA geometry that is slightly

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bent because of the constraints imposed by the nanocage structures. Interactions Modulating the Conformational Variability of the Linkers. The structural organization of the linkers in all three nanocages has been analyzed in detail in order to identify their contribution to the definition and stabilization of cages 3T, 5T, and 7T. The analysis indicates that the individual thymidines of the linker regions can interact one with the other mainly through two kinds of interactions, namely hydrogen bonds (HBs) or base stackings (BSs) between two or more thymidine rings. On the other hand the so-called T-shaped conformation, reported to occur in thymidine containing segments,35,36 is not so frequent in our simulations and represents only a transient assembly evolving toward nucleotides stacking. In line, the ΔG value reflecting the equilibrium between T-shaped or not T-shaped conformations (see Methodology) is always positive (ranging from 0 to 7 kcal/mol) for each linker of the three nanocages (Figure S4 of the Supporting Information). In Figure 5 the 24 linkers, present in each cage, are shown depicting the 6 “square faces” they build up in each cage (Figure 5A). In each square face built by the 3T, 5T, or 7T linker regions (Figure 5, parts BD) the hydrogen bonds and stacking thymidines, which are present for more than 50 and 70% of the simulation time, respectively, are represented by dashed lines and circles, respectively. The thymidines engage two main types of HBs that either involve two thymidines localized on different linker regions within the same “square face” (interlinker HBs) or two thymidines localized on the same linker region (intralinker HBs). The only interlinker HBs observed involve two thymidines, each belonging to one of the two linkers that branch from the same extremity of one helix (i.e., the HB connecting thymidine 1 and 3 in cage 3T of square face VI in Figure 5B). This interaction stabilizes the cage since it permits the formation of two HBs involving N3 atoms of both thymidines as donors and the O2 or the O4 atom of the other as acceptors (Figure 6A). At the same time the HBs favor a BS interaction between these thymidines and the two bases that constitute the final base pair of the helix from which the linker regions branch (Figure 6A). These interactions confer strong constraints on the relative orientation of the thymidines, generating a smaller conformational variability of the cage with 3T linkers (Figure 6B) compared to cages with longer linkers. In line with the linkers rigidity, the 3T double helices show a lower propensity to rotate as indicated by the flatness and the lower values of the global RMSFs (Figure 4A), as compared to the cage 5T (Figure 4B) and 7T (Figure 4C). On the other hand, the intralinker HBs are more frequent in the 5T and 7T cages (Figure 5, panels C and D, respectively), indicating that long linkers generate, during the simulation, compact substructures that induce a rotation of the double helices (Figure 4, panels BD). The other frequently observed interaction is the BS of two adjacent thymidines in the same linker. BS interactions, depicted in Figure 6 and Table S4 of the Supporting Information, are less frequent in cage 3T (Figure 5B and Figure 6B) than in cage 5T and cage 7T (Figures 5, panels C and D, and 6C) where, due to the large number of thymidines, multiple BS interactions are observed. In line, the ΔG value corresponding to the equilibrium between stacked or not stacked conformations indicates that in the 3T cage there are eight linkers with positive ΔGS values, only one in the 5T cage, and none in the 7T cage (Figure S5 of Supporting Information). 16824


Figure 7. Results of the linker cluster analysis for the 3T (A), 5T (B), and 7T (C) nanocages. Each linker is represented by a bar, and in each bar, the percentage of the three most populated clusters is reported. The most populated cluster is represented by the red color, and the intermediate and lowest populated ones are represented by the green and blue colors, respectively.

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The Journal of Physical Chemistry C The presence of HBs and BSs interactions between the thymidines confers constraints to the cages so that only a limited number of conformations are permitted. For each cage, the degree of conformational variability present in each linker region has been evaluated by separately clustering each linker in the three trajectories. The percentages of the three most populated clusters are reported in Figure 7. The results indicate that in the cage 3T (Figure 7A) each linker region samples only a limited number of conformations, since in each linker most of the conformations belong to the most representative cluster for more than 80% of the simulation time. The behavior is different for the cage 5T (Figure 7B) and cage 7T (Figure 7C) where in each linker several conformations populate a single cluster for a relatively short time, confirming that the degree of conformational variability is larger in cage 5T and cage 7T if compared with cage 3T.

’ CONCLUSIONS The results obtained in this work demonstrate that the DNA double helices are very stable in all of the analyzed cages and that the linker regions give a significant contribution to the final organization of the nanocage scaffold geometry. The total RMSD (Figure 2) and the gyration radius (Figure S2) show that for cages 3T, 5T, and 7T the starting truncated octahedron geometry, even though slightly distorted, is maintained along the entire trajectory. The comparison between the RMSDs calculated over the double helices and the thymidine linkers indicates that, in the global structure, the largest displacement is experienced by the thymidine strands that change conformations establishing HB and BS interactions. The local stability of every double helix is confirmed by the low RMSF values of the bases, when calculated separately for each helix (Figure 3), whereas when calculated on the entire structure it reveals the presence of a slight rotational motion that occurs around an axis tangential to the external border of the helix roughly parallel to the main helix axis (Figure 4, panels AD) mainly induced by the linkers rearrangements. In fact, during the simulations, the 5T and 7T thymidine linkers modify the extended structure, generated by the modeling procedure, shortening their length and exploring a large number of conformations (Figure 7, panels B and C). The reduction of the linkers length, caused by the establishment of HB and BS interactions, drags the helices extremities generating the double helices rotation (Figure 4D) and the general nanocage contraction (Figure 4, panels B and C). This phenomenon is less present in the 3T linkers that stay rather close to their initial extended structure exploring a small number of conformations (Figure 7A) and so having a low degree of double helices rotation (Figure 4A). The double helices remain stable over all of the trajectory for all three nanostructures, as shown by the RMSD from an ideal B-DNA helix for each single helix (Figure S3) and by the DNA geometrical parameters (Tables S1, S2, and S3 of the Supporting Information), indicating that the variety of conformations assumed by the linkers during the trajectory are not able to significantly alter the internal geometry and stability of the double helices. Free energy calculations indicate that the thymidine stacking represents the main stabilizing interaction that is enhanced by the linker length (Figure S5), whereas the T-shaped conformation corresponds to a transient state shifting toward a stable stacked conformation (Figure S4). The interactions occurring at the level of the linker constrain the conformational variability that is more

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limited in the cage 3T than in cages 5T and 7T as shown by the percentage of family clusters populated by each linker (Figure 7). The number of thymidines in the linker is then the element that, by modulating the number of base stacking and hydrogen bonds, confers a different degree of variability in the three cages and generates a conformational rearrangement of the double helices composing the nanostructure. As a final consideration it should be mentioned that the number of thymidines composing the linkers of the truncated octahedral DNA nanocages is responsible for the helices orientations, and this property may be used in future experiments to constrain specific helices regions to have an external accessibility.

’ ASSOCIATED CONTENT

bS Supporting Information. Additional figures and tables. This material is available free of charge via the Internet at http:// pubs.acs.org. ’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]. Phone: +39-(0)6-72594376. Fax: +39-(0)6-2022798. Present Addresses # Instituto de Física, Universidade de S~ao Paulo, Caixa Postal 66318, 05314970 S~ao Paulo, Brasil.

’ ACKNOWLEDGMENT The authors thank CASPUR research center of Rome, Italy (Inter Universities Consortium for Supercomputing Applications) for use of the MATRIX parallel computer. O.F. thanks Filas for a fellowship granted under the project ‘‘Caratterizzazione di principi attivi’’. ’ REFERENCES (1) Chen, J.; Seeman, N. Nature 1991, 350, 631–633. (2) Andersen, E. S.; Dong, M.; Nielsen, M. M.; Jahn, K.; Lind-Thomsen, A.; Mamdouh, W.; Gothelf, K. V.; Besenbacher, F.; Kjems, J. ACS Nano 2008, 2, 1213–1218. (3) Rothemund, P. Nature 2006, 440, 297–302. (4) Voigt, N. V.; Torring, T.; Rotaru, A.; Jacobsen, M. F.; Ravnsbaek, J. B.; Subramani, R.; Mamdouh, W.; Kjems, J.; Mokhir, A.; Besenbacher, F.; Gothelf, K. V. Nat. Nanotechnol. 2010, 5, 200–203. (5) Yan, H.; Park, S. H.; Finkelstein, G.; Reif, J.; LaBean, T. H. Science 2003, 301, 1882–1884. (6) LaBean, T. H.; Yan, H.; Kopatsch, J.; Liu, F.; Winfree, E.; Reif, J. H.; Seeman, N. C. J. Am. Chem. Soc. 2000, 122, 1848–1860. (7) Mathieu, F.; Liao, S.; Kopatsch, J.; Wang, T.; Mao, C.; Seeman, N. Six-Helix Bundles Designed from DNA. Nano Lett. 2005, 5, 661–665. (8) Aldaye, F.; Sleiman, H. J. Am. Chem. Soc. 2007, 129, 13376–13377. (9) Andersen, F.; Knudsen, B.; Oliveira, C.; Frøhlich, R.; Kr€uger, D.; Bungert, J.; Agbandje-McKenna, M.; McKenna, R.; Juul, S.; Veigaard, C.; Koch, J.; Rubinstein, J. L.; Guldbrandtsen, B.; Hede, M. S.; Karlsson, G.; Andersen, A. H.; Pedersen, J. S.; Knudsen, B. Nucleic Acids Res. 2008, 36, 1113–1119. (10) Bhatia, D.; Mehtab, S.; Krishnan, R.; Indi, S.; Basu, A.; Krishnan, Y. Angew. Chem., Int. Ed. 2009, 48, 4134–4137. (11) Goodman, R. P.; Schaap, I. A. T.; Tardin, C. F.; Erben, C. M.; Berry, R. M.; Schmidt, C. F.; Turberfield, A. J. Science 2005, 310, 1661–1665. 16826



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Simulative Analysis of a Truncated Octahedral DNA Nanocage Family

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