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Modulating Mobility: a Paradigm for Protein Engineering?

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Abstract

Proteins are highly mobile structures. In addition to gross conformational changes occurring on, for example, ligand binding, they are also subject to constant thermal motion. The mobility of a protein varies through its structure and can be modulated by ligand binding and other events. It is becoming increasingly clear that this mobility plays an important role in key functions of proteins including catalysis, allostery, cooperativity, and regulation. Thus, in addition to an optimum structure, proteins most likely also require an optimal dynamic state. Alteration of this dynamic state through protein engineering will affect protein function. A dramatic example of this is seen in some inherited metabolic diseases where alternation of residues distant from the active site affects the mobility of the protein and impairs function. We postulate that using molecular dynamics simulations, experimental data or a combination of the two, it should be possible to engineer the mobility of active sites. This may be useful in, for example, increasing the promiscuity of enzymes. Thus, a paradigm for protein engineering is suggested in which the mobility of the active site is rationally modified. This might be combined with more “traditional” approaches such as altering functional groups in the active site.

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Acknowledgments

MM thanks the Department of Employment and Learning, Northern Ireland (DELNI, UK) for a PhD studentship.

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Authors and Affiliations

  1. School of Biological Sciences, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK

    Margaret McAuley & David J. Timson

  2. School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK

    David J. Timson

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  1. Margaret McAuley
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  2. David J. Timson
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Correspondence to David J. Timson.

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McAuley, M., Timson, D.J. Modulating Mobility: a Paradigm for Protein Engineering?. Appl Biochem Biotechnol 181, 83–90 (2017). https://doi.org/10.1007/s12010-016-2200-y

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