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Using Molecular Simulation to Guide Protein Engineering for Biocatalysis in Organic Solvents

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Enzyme Engineering

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2397))

Abstract

Biocatalysis in organic solvents (OSs) is very appealing for the industry in producing bulk and/or fine chemicals, such as pharmaceuticals, biodiesel, and fragrances. The poor performance of enzymes in OSs (e.g., reduced activity, insufficient stability, and deactivation) negates OSs’ excellent solvent properties. Molecular dynamics (MD) simulations provide a complementary method to study the relationship between enzymes dynamics and the stability in OSs. Here we describe computational procedure for MD simulation of enzymes in OSs with an example of Bacillus subtilis lipase A (BSLA) in dimethyl sulfoxide (DMSO) cosolvent with software GROMACS. We discuss main essential practical issues considered (such as choice of force field, parameterization, simulation setup, and trajectory analysis). The core part of this protocol (enzyme-OS system setup, analysis of structural-based and solvation-based observables) is transferable to other enzymes and any OS systems. Combining with experimental studies, the obtained molecular knowledge is most likely to guide researchers to access rational protein engineering approaches to tailor OS resistant enzymes and expand the scope of biocatalysis in OS media. Finally, we discuss potential solutions to overcome the remaining challenges of computational biocatalysis in OSs and briefly draw future directions for further improvement in this field.

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Authors and Affiliations

  1. Lehrstuhl für Biotechnologie, RWTH Aachen University, Aachen, Germany

    Haiyang Cui, Markus Vedder, Ulrich Schwaneberg & Mehdi D. Davari

  2. DWI-Leibniz Institute for Interactive Materials, Aachen, Germany

    Haiyang Cui & Ulrich Schwaneberg

Authors
  1. Haiyang Cui
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  2. Markus Vedder
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  3. Ulrich Schwaneberg
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  4. Mehdi D. Davari
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Correspondence to Mehdi D. Davari .

Editor information

Editors and Affiliations

  1. Department of Biology and Biotechnology, University of Pavia, Pavia, Italy

    Francesca Magnani

  2. Department of Biology and Biotechnology, University of Pavia, Pavia, Italy

    Chiara Marabelli

  3. Department of Chemistry & Biochemistry, University of Bern, Bern, Switzerland

    Francesca Paradisi

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Cui, H., Vedder, M., Schwaneberg, U., Davari, M.D. (2022). Using Molecular Simulation to Guide Protein Engineering for Biocatalysis in Organic Solvents. In: Magnani, F., Marabelli, C., Paradisi, F. (eds) Enzyme Engineering. Methods in Molecular Biology, vol 2397. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1826-4_10

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  • DOI: https://doi.org/10.1007/978-1-0716-1826-4_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1825-7

  • Online ISBN: 978-1-0716-1826-4

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