Systems in which DNA is adsorbed onto gold nanoparticles have the potential for applications in gene regulation therapies, drug delivery, sensing, and DNA scaffolding. However, the mechanical stability of gold nanoparticles (AuNPs) and interfacial behavior between the gold nanoparticles and thiol ligands are not well understood or quantified. The stability of DNA-AuNP) systems is, therefore, examined using a large-scale specialized finite-element approach with a dislocation-density based crystalline plasticity framework to model the AuNPs and an elastic description to model thiol ligands, DNA, and the ionic solution. For compressive loading conditions, the system exhibited morphological instabilities in the nanoparticles, as well as high stress and dislocation-density gradients at the thiol-nanoparticle attachment sites, which can affect system stability and attachment strength.