A Peptide-Coated Gold Nanocluster Exhibits Unique Behavior in Protein Activity Inhibition

作者：Deyi An, Jiguo Su, Jeffrey K. Weber, Xueyun Gao, Ruhong Zhou, Jingyuan Li · 发表于：Journal of the American Chemical Society · 年份：2015 · DOI：10.1021/jacs.5b00888 · 被引用次数：93 · 研究领域：Nanocluster Synthesis and Applications、Gold and Silver Nanoparticles Synthesis and Applications、Advanced Nanomaterials in Catalysis

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 Au25 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...