Abstract
Implementing DNA computing circuits using components tethered to a surface offers several advantages over using components that freely diffuse in bulk solution. However, automated computational modeling of tethered circuits is far more challenging than for solution-phase circuits, because molecular geometry must be taken into account when deciding whether two tethered species may interact. Here, we tackle this issue by translating a tethered molecular circuit into a constraint problem that encodes the possible physical configurations of the components, using a simple biophysical model. We use a satisfaction modulo theories (SMT) solver to determine whether the constraint problem associated with a given structure is satisfiable, which corresponds to whether that structure is physically realizable given the constraints imposed by the tether geometry. We apply this technique to example structures from the literature, and discuss how this approach could be integrated with a reaction enumerator to enable fully automated analysis of tethered molecular computing systems.
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Notes
- 1.
See the Supporting Information (available from the first author’s web page) for full details of the examples and corresponding constraints.
References
Zhang, D.Y., Seelig, G.: Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3(2), 103–113 (2011)
Chen, Y.-J., Dalchau, N., Srinivas, N., Phillips, A., Cardelli, L., Soloveichik, D., Seelig, G.: Programmable chemical controllers made from DNA. Nat. Nanotechnol. 8, 755–762 (2013)
Soloveichik, D., Seelig, G., Winfree, E.: DNA as a universal substrate for chemical kinetics. PNAS 107(12), 5393–5398 (2010)
Cook, M., Soloveichik, D., Winfree, E., Bruck, J.: Programmability of chemical reaction networks. In: Algorithmic Bioprocesses, pp. 543–584. Springer, Heidelberg (2009)
Lakin, M.R., Youssef, S., Cardelli, L., Phillips, A.: Abstractions for DNA circuit design. JRS Interface 9(68), 470–486 (2012)
Lakin, M.R., Youssef, S., Polo, F., Emmott, S., Phillips, A.: Visual DSD: a design and analysis tool for DNA strand displacement systems. Bioinformatics 27(22), 3211–3213 (2011)
Qian, L., Winfree, E.: Scaling up digital circuit computation with DNA strand displacement cascades. Science 332, 1196–1201 (2011)
Rothemund, P.W.K.: Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006)
Tikhomirov, G., Petersen, P., Qian, L.: Programmable disorder in random DNA tilings. Nat. Nanotechnol. 12, 251–259 (2017)
Bui, H., Miao, V., Garg, S., Mokhtar, R., Song, T., Reif, J.: Design and analysis of localized DNA hybridization chain reactions. Small 13(12), 1602983 (2017)
Muscat, R.A., Strauss, K., Ceze, L., Seelig, G.: DNA-based molecular architecture with spatially localized components. In: Proceedings of ISCA 13 (2013)
Dalchau, N., Chandran, H., Gopalkrishnan, N., Phillips, A., Reif, J.: Probabilistic analysis of localized DNA hybridization circuits. ACS Synth. Biol. 4(8), 898–913 (2015)
Walsh, A.S., Yin, H., Erben, C.M., Wood, M.J.A., Turberfield, A.J.: DNA cage delivery to mammalian cells. ACS Nano 5(7), 5427–5432 (2011)
Lakin, M.R., Petersen, R., Gray, K.E., Phillips, A.: Abstract modelling of tethered DNA Circuits. In: Murata, S., Kobayashi, S. (eds.) DNA 2014. LNCS, vol. 8727, pp. 132–147. Springer, Cham (2014). doi:10.1007/978-3-319-11295-4_9
Petersen, R.L., Lakin, M.R., Phillips, A.: A strand graph semantics for DNA-based computation. Theor. Comput. Sci. 632, 43–73 (2016)
Moura, L., Bjørner, N.: Z3: an efficient SMT solver. In: Ramakrishnan, C.R., Rehof, J. (eds.) TACAS 2008. LNCS, vol. 4963, pp. 337–340. Springer, Heidelberg (2008). doi:10.1007/978-3-540-78800-3_24
Jovanović, D., Moura, L.: Solving non-linear arithmetic. In: Gramlich, B., Miller, D., Sattler, U. (eds.) IJCAR 2012. LNCS (LNAI), vol. 7364, pp. 339–354. Springer, Heidelberg (2012). doi:10.1007/978-3-642-31365-3_27
Grun, C., Werfel, J., Zhang, D.Y., Yin, P.: DyNAMiC Workbench: an integrated development environment for dynamic DNA nanotechnology. JRS Interface 12, 20150580 (2015)
Genot, A.J., Zhang, D.Y., Bath, J., Turberfield, A.J.: Remote toehold: a mechanism for flexible control of DNA hybridization kinetics. J. Am. Chem. Soc. 133, 2177–2182 (2011)
Doye, J.P.K., Ouldridge, T.E., Louis, A.A., Romano, F., Šulc, P., Matek, C., Snodin, B.E.K., Rovigatti, L., Schreck, J.S., Harrison, R.M., Smith, W.P.J.: Coarse-graining DNA for simulations of DNA nanotechnology. Phys. Chem. Chem. Phys. 15, 20395–20414 (2013)
Dirks, R.M., Pierce, N.A.: An algorithm for computing nucleic acid base-pairing probabilities including pseudoknots. J. Comput. Chem. 25, 1295–1304 (2004)
Acknowledgments
This material is based upon work supported by the National Science Foundation under grants 1525553, 1518861, and 1318833. The authors thank Neil Dalchau and Rasmus Petersen for productive discussions.
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Lakin, M.R., Phillips, A. (2017). Automated, Constraint-Based Analysis of Tethered DNA Nanostructures. In: Brijder, R., Qian, L. (eds) DNA Computing and Molecular Programming. DNA 2017. Lecture Notes in Computer Science(), vol 10467. Springer, Cham. https://doi.org/10.1007/978-3-319-66799-7_1
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