Comparing proteins and nucleic acids for next-generation biomolecular engineering

Abstract

Nanostructures built from biomolecules such as proteins, DNA and RNA are attracting attention in many areas of biological and materials sciences. Such nanoscale engineering was pioneered with proteins, yet the use of DNA is rapidly gaining traction. What are the advantages of the different biopolymers and which is best suited for a given molecular structure, function or application? In this Review, we evaluate the different structural properties of proteins and nucleic acids, as well as possible designs and synthetic routes for functional nanostructures. By comparing protein engineering and DNA nanotechnology, we highlight molecular architectures that are relevant in biotechnology, biomedicine and synthetic biology research, and identify emerging areas for research such as hybrid materials composed of protein and DNA/RNA.

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Fig. 1: Proteins, DNA and RNA.
Fig. 2: Natural and engineered proteins and DNA nanostructures used for biomolecular recognition.
Fig. 3: Engineered biocatalysts.
Fig. 4: Natural and engineered proteins that fulfil structural and cytoskeletal roles.
Fig. 5: Rationally designed DNA nanostructures.
Fig. 6: Natural and engineered hybrid systems that combine proteins, DNA and RNA.

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Acknowledgements

Supported the EPSRC (EP/N009282/1), the BBSRC (BB/M025373/1, BB/N017331/1), the Leverhulme Trust (RPG-2017-015) and Oxford Nanopore Technologies. The authors thank Keith Fox, Birte Höcker, and Derek Woolfson for critically reading the manuscript and suggesting improvements, and Katya Ahmad for calculating the van der Waals volumes of amino acids and nucleotides, and suggesting improvements for Box 1.

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G.C.P. and S.H. researched literature and wrote the article. J.R.B. contributed to the discussion of the content and editing of the manuscript, and generated the illustrations.

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Correspondence to Stefan Howorka.

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Pugh, G.C., Burns, J.R. & Howorka, S. Comparing proteins and nucleic acids for next-generation biomolecular engineering. Nat Rev Chem 2, 113–130 (2018). https://doi.org/10.1038/s41570-018-0015-9

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