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A deoxyribozyme-based molecular automaton


We describe a molecular automaton, called MAYA, which encodes a version of the game of tic-tac-toe and interactively competes against a human opponent. The automaton is a Boolean network of deoxyribozymes that incorporates 23 molecular-scale logic gates and one constitutively active deoxyribozyme arrayed in nine wells (3×3) corresponding to the game board. To make a move, MAYA carries out an analysis of the input oligonucleotide keyed to a particular move by the human opponent and indicates a move by fluorescence signaling in a response well. The cycle of human player input and automaton response continues until there is a draw or a victory for the automaton. The automaton cannot be defeated because it implements a perfect strategy.

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Figure 1: Basic gate structures, derived from allosterically regulated deoxyribozyme E6.
Figure 2: Game tree for the symmetry-pruned tic-tac-toe and the corresponding Boolean formulas.
Figure 3: Schematic representation of the distribution of gates in the individual wells of the MAYA automaton.
Figure 4: A representative game.
Figure 5: A second representative game.

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We acknowledge support by the National Aeronautics Space Agency (NAS2-02039 to M.N.S), the National Institute of Health (NIBIB, RO1 EB000675-1 to M.N.S), the National Science Foundation (EIA-0218262 to M.N.S and D.S, and CCR-0219587 and CCR-0085792 to D.S.), Microsoft Research (D.S.) and Hewlett-Packard (gift 88425.1 to D.S). M.N.S. acknowledges the support by Searle Scholars Program (03-C-103). We particularly thank Donald W. Landry for continued support of this project. We are also grateful to Deepak Kapur, Stephanie Forrest, Robert Veroff, Cristopher Moore, Lance Williams, Benjamin Andrews, and Clint Morgan for helpful discussions, suggestions and support.

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Correspondence to Milan N Stojanovic.

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Stojanovic, M., Stefanovic, D. A deoxyribozyme-based molecular automaton. Nat Biotechnol 21, 1069–1074 (2003).

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