Computational prediction of the interaction between drugs and targets is a standing challenge in the field of drug discovery. A number of rather accurate predictions were reported for various binary drug-target benchmark datasets. However, a notable drawback of a binary representation of interaction data is that missing endpoints for non-interacting drug-target pairs are not differentiated from inactive cases, and that predicted levels of activity depend on pre-defined binarization thresholds. In this paper, we present a method called SimBoost that predicts continuous (non-binary) values of binding affinities of compounds and proteins and thus incorporates the whole interaction spectrum from true negative to true positive interactions. Additionally, we propose a version of the method called SimBoostQuant which computes a prediction interval in order to assess the confidence of the predicted affinity, thus defining the Applicability Domain metrics explicitly. We evaluate SimBoost and SimBoostQuant on two established drug-target interaction benchmark datasets and one new dataset that we propose to use as a benchmark for read-across cheminformatics applications. We demonstrate that our methods outperform the previously reported models across the studied datasets.