Deconstructing Electrostatics of Functionalized Metal Nanoparticles from Molecular Dynamics Simulations

Gold nanoparticles (NPs) with different surface functionalizations can selectively interact with specific proteins, allowing a wide range of possible applications in biotechnology and biomedicine. To prevent their tendency to aggregate and to modulate their interaction with charged biomolecules or substrates (e.g., for biosensing applications), they can be functionalized with charged groups, introducing a mutual interaction which can be modulated by changing the ionic strength of the solvent. In silico modeling of these systems is often addressed with low-resolution models, which must account for these effects in the, often implicit, solvent representation. Here, we present a systematic conformational dynamic characterization of ligand-coated gold nanoparticles with different sizes, charges, and functionalizations by means of atomistic molecular dynamics simulations. Based on these, we deconstruct their electrostatic properties and propose a general representation of their average-long-range interactions extendable to different sizes, charges, and ionic strengths. This study clarifies in detail the role of the different features of the NP (charge, size, structure) and of the ionic strength in determining the details of the interparticle interaction and represents the first step toward a general strategy for the parametrization of NP coarse-grained models able to account for varying ionic strengths. © 2023 The Authors. Published by American Chemical Society.