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Strategies for Increasing Protein Stability

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Protein Nanotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2073))

Abstract

The stability of wild-type proteins is often a hurdle to their practical use in research, industry, and medicine. The route to engineering stability of a protein of interest lies largely with the available data. Where high-resolution structural data is available, rational design, based on fundamental principles of protein chemistry, can improve protein stability. Recent advances in computational biology and the use of nonnatural amino acids have also provided novel rational methods for improving protein stability. Likewise, the explosion of sequence and structural data available in public databases, in combination with improvements in freely available computational tools, has produced accessible phylogenetic approaches. Trawling modern sequence databases can identify the thermostable homologs of a target protein, and evolutionary data can be quickly generated using available phylogenetic tools. Grafting features from those thermostable homologs or ancestors provides stability improvement through a semi-rational approach. Further, molecular techniques such as directed evolution have shown great promise in delivering designer proteins. These strategies are well documented and newly accessible to the molecular biologist, allowing for rapid enhancements of protein stability.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

    Peter G. Chandler, Sebastian S. Broendum, Blake T. Riley, Matthew A. Spence & Ashley M. Buckle

  2. Research School of Chemistry, Australian National University, Canberra, ACT, Australia

    Colin J. Jackson

  3. Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

    Sheena McGowan

Authors
  1. Peter G. Chandler
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  2. Sebastian S. Broendum
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  3. Blake T. Riley
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  4. Matthew A. Spence
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  5. Colin J. Jackson
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  6. Sheena McGowan
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  7. Ashley M. Buckle
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Corresponding author

Correspondence to Ashley M. Buckle .

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Editors and Affiliations

  1. School of Biological Sciences, The MacDiarmid Institute for Advanced Materials and Nanotechnology, School of Chemical Sciences, University of Auckland, Auckland, New Zealand

    Juliet A. Gerrard

  2. School of Biological Sciences, Department of Chemical and Materials Engineering, The MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Auckland, Auckland, New Zealand

    Laura J. Domigan

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Chandler, P.G. et al. (2020). Strategies for Increasing Protein Stability. In: Gerrard, J., Domigan, L. (eds) Protein Nanotechnology. Methods in Molecular Biology, vol 2073. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9869-2_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9869-2_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9868-5

  • Online ISBN: 978-1-4939-9869-2

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