title: A Peptide-Coated Gold Nanocluster Exhibits Unique Behavior in Protein Activity Inhibition.
abstract: 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 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.
authors.affiliation: †CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, PR China.|‡College of Science, Yanshan University, Qinhuangdao 066004, PR China.
authors.forename: Deyi
authors.initials: D
authors.lastname: An
authors.affiliation: ‡College of Science, Yanshan University, Qinhuangdao 066004, PR China.
authors.forename: Jiguo
authors.initials: J
authors.lastname: Su
authors.affiliation: §IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Weber
authors.affiliation: †CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, PR China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Gao
authors.affiliation: §IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States.|∥Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Soochow University, Suzhou 215123, PR China.|⊥Department of Chemistry, Columbia University, New York, New York 10027, United States.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: †CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, PR China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
mesh_terms: D020134:Catalytic Domain; D004058:Diffusion; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012492:Salts / Q000737:chemistry; D055672:Static Electricity; D013438:Sulfhydryl Compounds; D054481:Thioredoxin Reductase 1 / Q000737:chemistry; D013879:Thioredoxins / Q000737:chemistry
chemical_list: D010455:Peptides; D011506:Proteins; D012492:Salts; D013438:Sulfhydryl Compounds; C491203:TXN protein, human; D013879:Thioredoxins; D006046:Gold; D054481:Thioredoxin Reductase 1