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Designing artificial enzymes by intuition and computation

Nature Chemistry volume 2, pages 15–24 (2010)Cite this article

Abstract

The rational design of artificial enzymes, either by applying physico–chemical intuition of protein structure and function or with the aid of computational methods, is a promising area of research with the potential to tremendously impact medicine, industrial chemistry and energy production. Designed proteins also provide a powerful platform for dissecting enzyme mechanisms of natural systems. Artificial enzymes have come a long way from simple α-helical peptide catalysts to proteins that facilitate multistep chemical reactions designed by state-of-the-art computational methods. Looking forward, we examine strategies employed by natural enzymes that could be used to improve the speed and selectivity of artificial catalysts.

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Figure 1: From sequence to structure to function.
Figure 2: Helical designs with tertiary structure.
Figure 3: Stepwise oxygen binding to a binary-patterned four-helix bundle.
Figure 4: Retrostructural analysis and design of a dinuclear metalloprotein.
Figure 5: Design versus structure of a Zn2+ binding MBP.
Figure 6: Assembly line for the ROSETTA Enzymes.
Figure 7: Millisecond timescale motions in adenylate cyclase.

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Acknowledgements

VN acknowledges support from the NIH Director's New Innovator Award Program, 1-DP2-OD006478-01 and the NSF BMAT program DMR-0907273. RLK acknowledges supported by the following grants: MCB-0920448 from the NSF, MCB-5G12 RR03060 toward support for the NMR facilities at the City College of New York, P41 GM-66354 to the New York Structural Biology Center and infrastructure support from NIH 5G12 RR03060 from the National Center for Research Resources.

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  1. Robert Wood Johnson Medical School - UMDNJ Biochemistry, Center for Advanced Biotechnology and Medicine, 679 Hoes Lane West, Piscataway, 08854, New Jersey, USA

    Vikas Nanda

  2. City College of New York Physics, 160 Convent Avenue, New York, 10031, New York, USA

    Ronald L. Koder

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Correspondence to Vikas Nanda.

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Nanda, V., Koder, R. Designing artificial enzymes by intuition and computation. Nature Chem 2, 15–24 (2010). https://doi.org/10.1038/nchem.473

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