ABSTRACT Protein‐templated gold nanoclusters (Au NCs) provide an atomically precise platform for investigating ion‐protein interactions and bio‐template synthesis. However, the influence of protein conformational dynamics and soft molecular confinement on NCs formation is often overlooked. Here, we address this question using lysozyme, a protein with defined cysteine quantity and conformation sensitivity as template. Evidenced by circular dichroism, zeta potential measurements, and small‐angle neutron scattering, conformational changes in lysozyme, manifested as residue rearrangement, unfolding, oligomerization and globular loosening, collectively modulate local microenvironment, thereby governing the coordination and growth behavior of Au species. Ostwald ripening of NCs growth captured by time‐resolved optical spectroscopy and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry show atomic precision. Tuning conformation by pH, Au─S coordination and NCs ripening pathways are governed with distinct kinetic characteristics. Our findings demonstrate that dynamic conformation of the protein template actively governs ion coordination and NCs formation. Contrast to conventional heterogeneous catalyst systems, typically based on rigid, extended nanoparticle or single‐atom architectures, this work provides direct evidence that ripening can proceed within soft, biomolecular confinement and is modulated by conformation. This study expands the conceptual boundaries of classical ripening theory and provides a mechanistic framework for protein‐directed synthesis in soft and dynamic environments.
Liu et al. (Wed,) studied this question.