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Understanding Interactions of Functionalized Nanoparticles with Proteins: A Case Study on Lactate Dehydrogenase
Author(s) -
Stueker Oliver,
Ortega Van A.,
Goss Greg G.,
Stepanova Maria
Publication year - 2014
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201303639
Subject(s) - molecular dynamics , lactate dehydrogenase , biophysics , colloidal gold , nanoparticle , nanomaterials , enzyme , kinetics , chemistry , function (biology) , protein dynamics , nanotechnology , biochemistry , materials science , computational chemistry , biology , physics , quantum mechanics , evolutionary biology
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 ( V max ) and a trend towards a reduced affinity (increased K m ) for the β‐NAD binding site, while pyruvate enzyme kinetics ( K m and V max ) 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.