DNA by Design: De novo Computational Framework for DNA Sequence Design and Nanotechnology
DOI:
https://doi.org/10.13052/jsame2245-8824.2022.002Keywords:
DNAAbstract
Chemical analysis of metalized DNA has made it quite clear that traditional models of DNA thermodynamics are insufficient to predict and control self-assembly in the context of orthogonally-paired nucleotides. Recently, there has been an increase in reports of Watson-Crick assembly of DNA wires and nanostructures [1–4]. The ability to add or remove pairing rules between nucleobases toward non-Watson-Crick, or orthogonal, self-assembly alters the fundamental language of DNA assembly: this change in behavior necessitates an accompanying shift in computational design. We begin by exploring the state-of-the-art in DNA modeling, and include both sequence analysis and sequence design practices. We then start from first principles and establish a mathematical basis for heterostructure and ‘nmer’ analysis in connected DNA networks that operates without assumptions about nucleobase parity. A generalized search algorithm is then constructed in Matlab and implemented using evolutionary techniques. We then discuss DNA nanostructure design criteria, operation efficiency in differentially-connected networks, and the application of computationally-aided sequence design for nanotechnological applications. We design a double crossover DNA motif with a silver base pair modification as a test case, and demonstrate successful model implementation. In sum, we present a novel computational framework for geometry-informed optimization of DNA networks. This tool is meant to enable design of both linear and nonlinear polynucleotide assemblies with inherent modularity for base parity, metalation, or more exotic nucleotide substitutions that may arise from advances in synthetic biology, nanomaterials and nanomedicine.
Downloads
References
Mathieu, F. et al. Six-helix bundles designed from DNA. Nano letters 5, 661–665, (2005).
Zheng, J. et al. From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal. Nature 461, 74, (2009).
Wang, R., Palma, M., Penzo, E. and Wind, S. J. Lithographically directed assembly of one-dimensional DNA nanostructures via bivalent binding interactions. Nano Research 6, 409–417, (2013).
Wang, R., Liu, W. and Seeman, N. C. Prototyping nanorod control: a DNA double helix sheathed within a DNA six-helix bundle. Chemistry & biology 16, 862–867, (2009).
Rich, A. and Davies, D. R. A new two stranded helical structure: polyadenylic acid and polyuridylic acid. Journal of the American Chemical Society 78, 3548–3549, (1956).
Rosenberg, J. M. et al. Double helix at atomic resolution. Nature 243, 150–154, (1973).
Seeman, N. C., Sussman, J. L., Berman, H. M. and Kim, S. Nucleic acid conformation: Crystal structure of a naturally occurring dinucleoside phosphate (UpA). Nature New Biology 233, 90–92, (1971).
Crick, F. and Watson, J. Molecular structure of deoxypentose nucleic acids. Nature 171, 738–740, (1953).
Wang, J. C. Helical repeat of DNA in solution. Proceedings of the National Academy of Sciences 76, 200–203, (1979).
Ono, A. et al. Specific interactions between silver(I) ions and cytosine-cytosine pairs in DNA duplexes. Chem Commun (Camb), 4825–4827, (2008).
Miyake, Y. et al. MercuryII-mediated formation of thymine-HgII-thymine base pairs in DNA duplexes. J Am Chem Soc 128, 2172–2173, (2006).
Wang, A. H. J. et al. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature 282, 680, (1979).
Franklin, R. E. and Gosling, R. G. The structure of sodium thymonucleate fibres. I. The influence of water content. Acta Crystallographica 6, 673–677, (1953).
Leroy, J.-L., Guéron, M., Mergny, J.-L. and Hélène, C. Intramolecular folding of a fragment of the cytosine-rich strand of telomeric DNA into an i-motif. Nucleic acids research 22, 1600–1606, (1994).
Sen, D. and Gilbert, W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature 334, 364, (1988).
Seeman, N. C. Nucleic-Acid Junctions and Lattices. Journal of Theoretical Biology 99, 237–247, (1982).
Ding, B., Sha, R. and Seeman, N. C. Pseudohexagonal 2D DNA crystals from double crossover cohesion. Journal of the American Chemical Society 126, 10230–10231, (2004).
Winfree, E., Liu, F. R., Wenzler, L. A. and Seeman, N. C. Design and self-assembly of two-dimensional DNA crystals. Nature 394, 539–544, (1998).
Geary, C., Rothemund, P. W. and Andersen, E. S. RNA nanostructures. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345, 799–804, (2014).
Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302, (2006).
Wang, X. et al. An Organic Semiconductor Organized into 3D DNA Arrays by “Bottom-up” Rational Design. Angewandte Chemie International Edition 56, 6445–6448, (2017).
Mao, C. D., Sun, W. Q. and Seeman, N. C. Designed two-dimensional DNA Holliday junction arrays visualized by atomic force microscopy. Journal of the American Chemical Society 121, 5437–5443, (1999).
Dietz, H., Douglas, S. M. and Shih, W. M. Folding DNA into twisted and curved nanoscale shapes. Science 325, 725–730, (2009).
Zhang, Q. et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano 8, 6633–6643, (2014).
Pearson, A. C. et al. DNA origami metallized site specifically to form electrically conductive nanowires. J Phys Chem B 116, 10551–10560, (2012).
Zhao, Z., Jacovetty, E. L., Liu, Y. and Yan, H. Encapsulation of gold nanoparticles in a DNA origami cage. Angewandte Chemie International Edition 50, 2041–2044, (2011).
Seeman, N. C. De novo design of sequences for nucleic acid structural engineering. Journal of biomolecular structure and dynamics 8, 573–581, (1990).
Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic acids research 37, 5001–5006, (2009).
Zhu, J., Wei, B., Yuan, Y. and Mi, Y. UNIQUIMER 3D, a software system for structural DNA nanotechnology design, analysis and evaluation. Nucleic acids research 37, 2164–2175, (2009).
Kearse, M. et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649, (2012).
Oberortner, E., Cheng, J.-F., Hillson, N. J. and Deutsch, S. Streamlining the design-to-build transition with build-optimization software tools. ACS synthetic biology 6, 485–496, (2016).
Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic acids research 31, 3406–3415, (2003).
PrimerQuest®
program (IDT, Coralville, IA, USA, 2018).
Saiki, R. K. in PCR technology 7–16 (Springer, 1989).
Allawi, H. T. and SantaLucia, J. Thermodynamics and NMR of internal G ⊙
T mismatches in DNA. Biochemistry 36, 10581–10594, (1997).
Peyret, N., Seneviratne, P. A., Allawi, H. T. and SantaLucia, J., Jr. Nearest-neighbor thermodynamics and NMR of DNA sequences with internal A.A, C.C, G.G, and T.T mismatches. Biochemistry 38, 3468–3477, (1999).
Kaur, H., Arora, A., Wengel, J. and Maiti, S. Thermodynamic, Counterion, and Hydration Effects for the Incorporation of Locked Nucleic Acid Nucleotides into DNA Duplexes. Biochemistry 45, 7347–7355, (2006).
Xia, T. et al. Thermodynamic Parameters for an Expanded Nearest-Neighbor Model for Formation of RNA Duplexes with Watson-Crick Base Pairs. Biochemistry 37, 14719–14735, (1998).
Nakano, S.-i., Fujimoto, M., Hara, H. and Sugimoto, N. Nucleic acid duplex stability: influence of base composition on cation effects. Nucleic acids research 27, 2957–2965, (1999).
Owczarzy, R., Moreira, B. G., You, Y., Behlke, M. A. and Walder, J. A. Predicting stability of DNA duplexes in solutions containing magnesium and monovalent cations. Biochemistry 47, 5336–5353, (2008).
Vecchioni, S., Capece, M. C., Toomey, E., Rothschild, L. and Wind, S. J. Methods of Synthesis and Characterization of Conductive DNA Nanowires Based on Metal Ion-Mediated Base Pairing for Single-Molecule Electronics. Journal of Self-Assembly and Molecular Electronics (SAME) 6, 61–90, (2018).
Dairaku, T. et al. Structure Determination of an AgI-Mediated Cytosine–Cytosine Base Pair within DNA Duplex in Solution with 1H/15N/109Ag NMR Spectroscopy. Chemistry-A European Journal 22, 13028–13031, (2016).
Torigoe, H. et al. Thermodynamic and structural properties of the specific binding between Ag(+) ion and C:C mismatched base pair in duplex DNA to form C-Ag-C metal-mediated base pair. Biochimie 94, 2431–2440, (2012).
Holland, J. H. Adaptation in natural and artificial systems: an introductory analysis with applications to biology, control, and artificial intelligence. (MIT press, 1992).
Konak, A., Coit, D. W. and Smith, A. E. Multi-objective optimization using genetic algorithms: A tutorial. Reliability Engineering & System Safety 91, 992–1007, (2006).
Wu, J.-S., Lee, C., Wu, C.-C. and Shiue, Y.-L. Primer design using genetic algorithm. Bioinformatics 20, 1710–1717, (2004).
Rinker, S., Ke, Y., Liu, Y., Chhabra, R. and Yan, H. Self-assembled DNA nanostructures for distance-dependent multivalent ligand–protein binding. Nature nanotechnology 3, 418, (2008).
Liu, D., Park, S. H., Reif, J. H. and LaBean, T. H. DNA nanotubes self-assembled from triple-crossover tiles as templates for conductive nanowires. Proceedings of the National Academy of Sciences 101, 717–722, (2004).
Seeman, N. C. DNA nicks and nodes and nanotechnology. Nano letters 1, 22–26, (2001).
Fardian-Melamed, N. et al. Electronic Level Structure of Silver-Intercalated Cytosine Nanowires. Nano Letters, (2020).
Livshits, G. I. et al. Long-range charge transport in single G-quadruplex DNA molecules. Nature nanotechnology 9, 1040–1046, (2014).
Hush, N. and Cheung, A. S. Ionization potentials and donor properties of nucleic acid bases and related compounds. Chemical Physics Letters 34, 11–13, (1975).
