Molecular Recognition by Gold Nanoparticle-Based Receptors as Defined through Surface Morphology and Pockets Fingerprint

[Image: see text] Ligand shell-protected gold nanoparticles can form nanoreceptors that recognize and bind to specific molecules in solution, with numerous potential innovative applications in science and industry. At this stage, the challenge is to rationally design such nanoreceptors to optimize their performance and boost their further development. Toward this aim, we have developed a new computational tool, Nanotron. This allows the analysis of molecular dynamics simulations of ligand shell-protected nanoparticles to define their exact surface morphology and pocket fingerprints of binding cavities in the coating monolayer. Importantly, from dissecting the well-characterized pairing formed by the guest salicylate molecule and specific host nanoreceptors, our work reveals that guest binding at such nanoreceptors occurs via preformed deep pockets in the host. Upon the interaction with the guest, such pockets undergo an induced-fit-like structural optimization for best host–guest fitting. Our findings and methodological advancement will accelerate the rational design of new-generation nanoreceptors.