Gold nanoparticles (AuNPs) are employed as drug carriers due to their inertness, non-toxicity, and ease of synthesis. An experimental search for the optimal AuNP design would require a systematic variation of physico-chemical properties which is time-consuming and expensive. Computational methods provide quicker and cheaper approach to complement experiments and provide useful guidelines. In this paper, we performed atomistic molecular dynamics simulations to study how the size, hydrophobicity, and concentration of the drug affect the structure of functionalized AuNPs in the aqueous environment. We simulated two groups of nano-systems functionalized with a zwitterionic background ligand, and a ligand carrying a drug (Quinolinol or Panobinostat). Results indicate that in the case of a hydrophobic drug (Quinolinol), the hydrophobicity drives the conformation changes of the coating layer. The tendency of the hydrophobic drug to reduce its solvent-accessible surface results in a decrease of the coating thickness and the overall NP size. Although the amount of accessible drug can be increased by increasing its initial concentration, it will compromise the solubility of the system. In the case of a hydrophilic drug (Panobinostat), the ligand in excess has a dominant influence on the final structure of the coating conformations. The percentage of accessible drug is significantly higher than in the hydrophobic systems for any given ratio. It implies that for hydrophilic systems we can generally expect higher biological efficiency. Our results highlight the importance of taking into account physico-chemical properties of drugs and ligands when developing gold-based nanosystems, especially in the case of hydrophobic drugs
