Design Rules for Selective Peptide Amphiphile-Gold Nanoparticle Interactions from Atomistic Simulations

Peptide amphiphiles (PAs) offer modular control over biomineralization, yet the mechanisms by which they guide nanoparticle growth at the water-metal interface remain poorly understood. We employ molecular dynamics coupled with enhanced sampling methods to dissect residue-level interactions, component contributions, and full PA adsorption on Au(111) and Au(100). Using a modular PA incorporating the Au-binding Flg peptide (DYKDDDDK), we show that tyrosine dominates Au(111) adsorption, while charged residues largely remain in the adsorbed water layers. For individual amino acids and the beta-sheet forming region, orientation-resolved free energy landscapes reveal prominent backbone participation in adsorption to Au(111). In contrast, adsorption of the full Flg peptide and Flg-PA is dominated by the tyrosine side chain, with the peptide backbone remaining in solution. Cooperative effects among neighboring residues rationalize Flg's mineralizing capacity: the presence of at least one adjacent lysine enhances Tyr-mediated Au(111) adsorption, while a purely acidic local environment diminishes facet selectivity. The results provide the first atomically detailed framework for PA-Au interactions, providing guiding principles for future PA-based nanomaterial engineering.