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Training a molecular automaton to play a game


Research at the interface between chemistry and cybernetics has led to reports of ‘programmable molecules’, but what does it mean to say ‘we programmed a set of solution-phase molecules to do X’? A survey of recently implemented solution-phase circuitry1,2,3,4,5,6,7,8,9,10,11,12,13,14,15 indicates that this statement could be replaced with ‘we pre-mixed a set of molecules to do X and functional subsets of X’. These hard-wired mixtures are then exposed to a set of molecular inputs, which can be interpreted as being keyed to human moves in a game, or as assertions of logical propositions. In nucleic acids-based systems, stemming from DNA computation16,17,18,19,20, these inputs can be seen as generic oligonucleotides. Here, we report using reconfigurable21,22,23 nucleic acid catalyst-based units to build a multipurpose reprogrammable molecular automaton that goes beyond single-purpose ‘hard-wired’ molecular automata. The automaton covers all possible responses to two consecutive sets of four inputs (such as four first and four second moves for a generic set of trivial two-player two-move games). This is a model system for more general molecular field programmable gate array (FPGA)-like devices that can be programmed by example, which means that the operator need not have any knowledge of molecular computing methods.

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Figure 1: Schematic presentation of the game of tit-for-tat.
Figure 2: Basic molecular logic units and their activation during training and game play.
Figure 3: Demonstration of training and play-back.


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This material is based upon work supported by the National Science Foundation. M.N.S. is a Lymphoma and Leukemia Society Fellow. The authors are grateful to P. Jelenkovic and N. Dabby for comments and advice.

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Authors and Affiliations



R.P. supervised and coordinated experimental efforts, optimized gates, performed the majority of experiments, analysed results and participated in writing the paper. E.M. participated in the initial ideation of the game, performed experiments and analysed results. M.L. performed experiments and analysed results. D.S. performed the game strategy analysis computationally, ran simulations and participated in writing the paper. M.N.S. initiated the project, proposed the game with E.M., and wrote the initial version of the paper.

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Correspondence to Milan N. Stojanovic.

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The authors declare no competing financial interests.

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Pei, R., Matamoros, E., Liu, M. et al. Training a molecular automaton to play a game. Nature Nanotech 5, 773–777 (2010).

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