Abstract
Elucidation of the driving forces that govern interactions between nanoparticles and intrinsically disordered proteins (IDP) is important for the understanding of the effect of nanoparticles in living systems and for the design of new nanoparticle-based assays to monitor health and combat disease. The quantitative interaction profile of the intrinsically disordered transactivation domain of p53 and its mutants with anionic silica nanoparticles is reported at atomic resolution using nuclear magnetic spin relaxation experiments. These profiles are analyzed with a novel interaction model that is based on a quantitative nanoparticle affinity scale separately derived for the 20 natural amino acids. The results demonstrate how the interplay of attractive and repulsive Coulomb interactions with hydrophobic effects is responsible for the sequence-dependent binding of a disordered protein to nanoparticles.