This chapter presents a methodology to quantify the essential interactions at the bionano interface, which can be used in combination with the adverse outcome pathway analysis to build mechanism-based predictive schemes for toxicity assessments. It introduces a set of new, advanced descriptors of the nanomaterials, which refer to their ability to bind biomolecules and trigger the pathways via the molecular initiating events. Quantitative understanding of the interactions and structure of the bionano interface is, therefore, crucial to our ability to predict the probability of molecular initiating events for the specific e adverse outcome pathways and to relate it to the nanomaterial’s properties. Nanoparticles (NP) size, however, also plays a fundamental role in the formation of the corona and in the interactions at the bionano interface. The NP core plays a crucial role in the protein adsorption as it contains most of the nanomaterial. The new descriptors include those for proteins and those for interaction with NPs.