Molecular‐Dynamics‐Simulation‐Directed Rational Design of Nanoreceptors with Targeted Affinity

Here, we demonstrate the possibility of rationally designing nanoparticle receptors with targeted affinity and selectivity for specific small molecules. We used atomistic molecular‐dynamics (MD) simulations to gradually mutate and optimize the chemical structure of the molecules forming the coating monolayer of gold nanoparticles (1.7 nm gold‐core size). The MD‐directed design resulted in nanoreceptors with a 10‐fold improvement in affinity for the target analyte (salicylate) and a 100‐fold decrease of the detection limit by NMR‐chemosensing from the millimolar to the micromolar range. We could define the exact binding mode, which features prolonged contacts and deep penetration of the guest into the monolayer, as well as a distinct shape of the effective binding pockets characterized by exposed interacting points.