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CRN++: Molecular programming language

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Abstract

Synthetic biology is a rapidly emerging research area, with expected wide-ranging impact in biology, nanofabrication, and medicine. A key technical challenge lies in embedding computation in molecular contexts where electronic micro-controllers cannot be inserted. This necessitates effective representation of computation using molecular components. While previous work established the Turing-completeness of chemical reactions, defining representations that are faithful, efficient, and practical remains challenging . This paper introduces CRN++, a new language for programming deterministic (mass-action) chemical kinetics to perform computation. We present its syntax and semantics, and build a compiler translating CRN++ programs into chemical reactions, thereby laying the foundation of a comprehensive framework for molecular programming. Our language addresses the key challenge of embedding familiar imperative constructs into a set of chemical reactions happening simultaneously and manipulating real-valued concentrations. Although some deviation from ideal output value cannot be avoided, we develop methods to minimize the error, and implement error analysis tools. We demonstrate the feasibility of using CRN++on a suite of well-known algorithms for discrete and real-valued computation. CRN++ can be easily extended to support new commands or chemical reaction implementations, and thus provides a foundation for developing more robust and practical molecular programs.

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Notes

  1. Although certain pathological CRNs can drive concentrations to infinity in finite time (e.g., \(2A \rightarrow 3A\)), and thereby drive certain other species to 0 in finite time (e.g., with an additional \(B + A \rightarrow A\) ), these cases cannot be implemented with any reasonable chemistry.

  2. A problematic feature of this module is that the concentration of H increases without bound if [A] < [B]. Although this does not affect the correctness of the computation, it is an interesting open question whether there is another truncated subtraction module that satisfies composability and exhibits exponential convergence but has bounded concentrations for any input regime.

  3. This convergence happens irrespective of the initial concentrations of the flag species \(X_{gtY}\) and \(X_{ltY}\) (as long as they sum to 1), so they do not have to be reset before the mapping.

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Acknowledgements

We thank the fellow students of EE 381V (Programming With Molecules) at The University of Texas at Austin for constructive discussions on the material presented in this paper. We also thank Keenan Breik, Cameron Chalk, Milos Gligoric, Aleksandar Milicevic, Boya Wang and Kaiyuan Wang for their feedback on this work. This research was partially supported by the US National Science Foundation under Grants Nos. CCF-1618895, CCF-1718903, CCF-1652824, and CCF-1704790.

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  1. The University of Texas at Austin, Austin, USA

    Marko Vasić, David Soloveichik & Sarfraz Khurshid

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  1. Marko Vasić
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  2. David Soloveichik
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Correspondence to Marko Vasić.

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Vasić, M., Soloveichik, D. & Khurshid, S. CRN++: Molecular programming language. Nat Comput 19, 391–407 (2020). https://doi.org/10.1007/s11047-019-09775-1

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