The kinome-wide comparison is based on an all-against-all comparison of all available structures. Note that a kinase can be represented by multiple structures (see KLIFS data section), thus, a kinase pair can be represented by multiple structure pairs with multiple distance values. Our final goal is to assign one distance value to each kinase pair as a measure of the similarity between these two kinases (Figure ). The structural coverage of kinases is highly imbalanced: Some kinases are represented by one structure only, others like EGFR or CDK2 by more than 100. We select the structure pair with the lowest distance as representative for the kinase pair, hence always picking the two closest structures in the dataset. For example, if a dataset consists of ten structures representing three kinases, the 10 × 10 all-against-all structure distance matrix will be reduced to a 3 × 3 all-against-all kinase distance matrix, consisting of the lowest distance values only after mapping structure pairs to kinase pairs.