Molecular-Dynamics-Simulation-Directed Rational Design of Nanoreceptors with Targeted Affinity.
Xiaohuan SunLaura RiccardiFederico De BiasiFederico RastrelliMarco De VivoFabrizio MancinPublished in: Angewandte Chemie (International ed. in English) (2019)
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.
Keyphrases
- molecular dynamics
- molecular dynamics simulations
- density functional theory
- gold nanoparticles
- molecular docking
- cancer therapy
- capillary electrophoresis
- magnetic resonance
- dna binding
- photodynamic therapy
- high resolution
- binding protein
- loop mediated isothermal amplification
- transcription factor
- label free
- drug delivery
- protein kinase
- sensitive detection
- structural basis