2 research outputs found
A Peptide-Coated Gold Nanocluster Exhibits Unique Behavior in Protein Activity Inhibition
Gold
nanoclusters (AuNCs) can be primed for biomedical applications through
functionalization with peptide coatings. Often anchored by thiol groups,
such peptide coronae not only serve as passivators but can also endow
AuNCs with additional bioactive properties. In this work, we use molecular
dynamics simulations to study the structure of a tridecapeptide-coated
Au<sub>25</sub> cluster and its subsequent interactions with the enzyme
thioredoxin reductase 1, TrxR1. We find that, in isolation, both the
distribution and conformation of the coating peptides fluctuate considerably.
When the coated AuNC is placed around TrxR1, however, the motion of
the highly charged peptide coating (+5e/peptide) is quickly biased
by electrostatic attraction to the protein; the asymmetric coating
acts to guide the nanocluster’s diffusion toward the enzyme’s
negatively charged active site. After the AuNC comes into contact
with TrxR1, its peptide corona spreads over the protein surface to
facilitate stable binding with protein. Though individual salt bridge
interactions between the tridecapeptides and TrxR1 are transient in
nature, the cooperative binding of the peptide-coated AuNC is very
stable, overall. Interestingly, the biased corona peptide motion,
the spreading and the cooperation between peptide extensions observed
in AuNC binding are reminiscent of bacterial stimulus-driven approaching
and adhesion mechanisms mediated by cilia. The prevailing AuNC binding
mode we characterize also satisfies a notable hydrophobic interaction
seen in the association of thioredoxin to TrxR1, providing a possible
explanation for the AuNC binding specificity observed in experiments.
Our simulations thus suggest this peptide-coated AuNC serves as an
adept thioredoxin mimic that extends an array of auxiliary structural
components capable of enhancing interactions with the target protein
in question
Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating
The advent and pending wide use of nanoscale materials urges a biosafety assessment and safe design of nanomaterials that demonstrate applicability to human medicine. In biological microenvironment, biomolecules will bind onto nanoparticles forming corona and endow nanoparticles new biological identity. Since blood-circulatory system will most likely be the first interaction organ exposed to these nanomaterials, a deep understanding of the basic interaction mechanisms between serum proteins and foreign nanoparticles may help to better clarify the potential risks of nanomaterials and provide guidance on safe design of nanomaterials. In this study, the adsorption of four high-abundance blood proteins onto the carbon-based nanomaterial graphene oxide (GO) and reduced GO (rGO) were investigated <i>via</i> experimental (AFM, florescence spectroscopy, SPR) and simulation-based (molecular dynamics) approaches. Among the proteins in question, we observe competitive binding to the GO surface that features a mélange of distinct packing modes. Our MD simulations reveal that the protein adsorption is mainly enthalpically driven through strong π–π stacking interactions between GO and aromatic protein residues, in addition to hydrophobic interactions. Overall, these results were in line with previous findings related to adsorption of serum proteins onto single-walled carbon nanotubes (SWCNTs), but GO exhibits a dramatic enhancement of adsorption capacity compared to this one-dimensional carbon form. Encouragingly, protein-coated GO resulted in a markedly less cytotoxicity than pristine and protein-coated SWCNTs, suggesting a useful role for this planar nanomaterial in biomedical applications