Modeling Interactions of Functionalized Nanoparticles with Biological Receptors

O. Stueker, M. Stepanova
National Institute for Nanotechnology, National Research Council of Canada, CA

Keywords: gold nanoparticle, essential collective dynamics, LDH, molecular dynamics, protein conformations, multiscale modelig


Understanding the interactions between functionalized metallic nanoparticles and biological components can give insight into the molecular mechanisms of toxicity of nanomaterials. We have developed a detailed molecular dynamics (MD) model of an alkyl-thiol (AT) functionalized gold nanoparticle with a diameter of ~4.3 nm in solution. According to recent experiments, such NPs can significantly reduce the activity of L‑lactate dehydrogenase (LDH). To study the NP-LDH interactions and the inhibition of LDH on a molecular level, the NP and LDH are simulated both individually and in contact with each other. In order to analyze the NP-LDH complex, the recently developed method of Essential Collective Dynamics (ECD) is employed, which has earlier been validated by comparison with NMR experiments, and proven to provide an accurate assessment of dynamical coarse-grained structure and local flexibility in biopolymers based on relatively short MD trajectories. We have studied the structure of the AT brush on NP’s surface, and demonstrated that it tends to form bundles of highly correlated AT-chains. We further analyzed the impact of NP binding on the intra-molecular correlations and main-chain flexibility in LDH and report our extensive and detailed study of the correlations which characterize the molecular mechanisms of binding in the NP-LDH complex.