Similar to the approach of Alves et al. , for virtual screening of the DrugBank and building of a web tool formulations were classified as being within the applicability domain (AD) if their Euclidean distance to TS compounds within the multidimensional, scaled descriptor space was below a pre-defined threshold D cutoff . The latter was determined by the average distance < D > and the corresponding standard deviation s based on all mixtures of the TS to its k nearest neighbors . Modeling steps for the final models were repeated with Y-randomization in order to assess possible chance correlations . Feature importance was assessed by computing Shapley (SHAP) values via the KernelSHAP algorithm . Stemming from game theory , these values evaluate the contribution of descriptors to single model outcomes taking into account interactions between the different features.