摘要:SummaryMolecular conformational engineering is to engineer flexible non-functional molecules into unique conformations to create novel functions just like natural proteins fold. Obviously, it is a grand challenge with tremendous opportunities. Based on the facts that natural proteins are only marginally stable with a net stabilizing energy roughly equivalent to the energy of two hydrogen bonds, and the energy barriers for the adatom diffusion of some metals are within a similar range, we propose that metal nanoparticles can serve as a general replacement of protein scaffolds to conformationally engineer protein fragments on the surface of nanoparticles. To prove this hypothesis, herein, we successfully restore the antigen-recognizing function of the flexible peptide fragment of a natural anti-lysozyme antibody on the surface of silver nanoparticles, creating a silver nanoparticle-base artificial antibody (Silverbody). A plausible mechanism is proposed, and some general principles for conformational engineering are summarized to guide future studies in this area.Graphical abstractDisplay OmittedHighlights•A silver NP-based artificial antibody is created by conformational engineering•Function emerges on NPs from non-functional peptide by mimicking the protein folding•A general mechanism is proposed for the conformational engineering on metal NPsEngineering, Nanoparticles, Diffusion potentials