Understanding interactions of functionalized nanoparticles with proteins: A case study on lactate dehydrogenase

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DOIResolve DOI: http://doi.org/10.1002/smll.201303639
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Journal titleSmall
Pages20062021; # of pages: 16
SubjectBiomedical engineering; Chains; Computer simulation; Enzyme activity; Enzyme kinetics; Gold; Medical nanotechnology; Metal nanoparticles; Molecular dynamics; Nanostructured materials; Reaction kinetics; Enzyme functions; Functionalized gold nanoparticles; Functionalized nanoparticles; Lactate dehydrogenase; Molecular dynamics simulations; Molecular simulations; Structural and dynamic properties; toxicology; Proteins
AbstractNanomaterials 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. Using molecular dynamic simulations for single, functionalized nanoparticles in solution and a newly developed method of analysis, Stueker and co-workers describe the effects of binding of a mercapto-undecanoic acid functionalized 4.2 nm gold nanoparticle on the structural and dynamic properties of the biological enzyme LDH. The predictions help to explain the experimentally determined alterations in measured LDH enzyme activity when exposed to these particles. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21272281
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Record identifier17760257-7832-4c62-b448-36e7cd2d9522
Record created2014-07-23
Record modified2016-05-09
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