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Understanding Interactions of Functionalized Nanoparticles with Proteins: A Case Study on Lactate Dehydrogenase

Authors

  • Oliver Stueker,

    1. National Institute for Nanotechnology, National Research Council of Canada, EdmontonAlberta, Canada
    2. Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada
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  • Van A. Ortega,

    1. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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  • Greg G. Goss,

    1. National Institute for Nanotechnology, National Research Council of Canada, EdmontonAlberta, Canada
    2. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
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  • Maria Stepanova

    Corresponding author
    1. National Institute for Nanotechnology, National Research Council of Canada, EdmontonAlberta, Canada
    2. Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada
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Abstract

Nanomaterials in biological solutions are known to interact with proteins and have been documented to affect protein function, such as enzyme activity. Understanding the interactions of nanoparticles with biological components at the molecular level will allow for rational designs of nanomaterials for use in medical technologies. Here we present the first detailed molecular mechanics model of functionalized gold nanoparticle (NP) interacting with an enzyme (l-lactate dehydrogenase (LDH) enzyme). Molecular dynamics (MD) simulations of the response of LDH to the NP binding demonstrate that although atomic motions (dynamics) of the main chain exhibit only a minor response to the binding, the dynamics of side chains are significantly constrained in all four active sites that predict alteration in kinetic properties of the enzyme. It is also demonstrated that the 5 nm gold NPs cause a decrease in the maximal velocity of the enzyme reaction (Vmax) and a trend towards a reduced affinity (increased Km) for the β-NAD binding site, while pyruvate enzyme kinetics (Km and Vmax) are not significantly altered in the presence of the gold NPs. These results demonstrate that modeling of NP:protein interactions can be used to understand alterations in protein function.

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