The interaction between proteins and nanoparticles (NPs) is central to many aspects of nanoscience and nanotechnological applications. NPs have been reported to either affect or leave unchanged protein structure and function, depending on the specific properties of the NPs surface and dimensions, the environmental conditions, the actual protein characteristics. Particular relevance has been attributed to the interaction of NPs with amyloidogenic proteins due to the interest in possible therapeutic approaches for a class of pathologies with poor treatment, if any.
We present recent computational modeling advances which were pursued in the quest for a theoretical framework elucidating the association mechanisms and the ability to design and control the recognition capability of β2-microglobulin and its two amyloidogenic variants, towards: (i) 5 nm hydrophilic citrate-capped gold NPs, (ii) 2.5 nm gold NPs functionalized with hydrophobic organic ligands and (iii) glycosaminoglycans charge arrays. Recent simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson_Boltzmann electrostatics) and NMR measurements explains the origin of the observed protein perturbations in the presence of citrate-capped gold NPs. Experiments have shown that the interaction is weak in the physiological-like, conditions and it is not able to induce protein fibrillation. On the contrary, binding of the protein to hydrophobic ligands can be stronger and able to block the active sites of domain from binding to another protein, thus inhibiting the fibrillation activity.