Chiral Ligand-Protected Gold Nanoclusters as Biosensors for Small Chiral Biomolecules: A Computational Study

Detection of chiral biomolecules in biological environments presents an important challenge: to develop sensitive, noninvasive sensors that Could have an impact in several areas such as drug discovery, diagnostics of diseases, and care. In this work, we introduce a strategy for experimentally realizable, noninvasive sensing of small chiral biomolecules in aqueous solvents, validated via classical force-field molecular dynamics simulations and density functional theory calculations. We investigated the interactions of the L/D forms of glutathione and seven chiral amino acids (Ala, Arg, Asp, Cys, Glu, Ser, Tyr) with six chiral, water-soluble, thiolate-protected gold nanoclusters in the range of 25-144 gold atoms, via dynamical sampling extending up to 3 μs time scales in water at neutral pH. We found surprisingly large variations in the binding probability (from <1% to 100%) of these analytes to the nanoclusters, with the dominating interaction being electrostatics between the analyte and the nanoclusters' ligand surface, augmented by hydrogen bonding and van der Waals interactions. Computed circular dichroism spectra for several nanocluster-analyte complexes predict the identification of analyte-specific adsorption events and even the resolution of the adsorbed enantiomer in selected cases, constituting an experimentally realizable sensing function. Our results suggest that chiral ligand-protected gold nanoclusters could be used for noninvasive chiral sensing, creating a tunable toolbox where the nanocluster size and chiral ligand type could be varied for optimizing the sensing activity for specific targets.