The KiSSim fingerprint contains physicochemical bits, which generalize the pocket sequence, and spatial bits, which consider the individual atom/residue positions in the under- (a) Highlight residues with at least one large difference in their physicochemical bits (∆d normalized = 0.6, blue), spatial bits (∆d normalized = 0.2, yellow), or both (green). Color residues by their differences in their (b) HBA, (c) aliphatic, and (d) hinge region feature, ranging from no difference (white) to highest difference (blue). See notebook for more details. lying kinase conformations. First, we use the KLIFS pocket sequence (KLIFS seq) to probe if the KiSSim fingerprint's generalized sequence and spatial information improve predictions compared to sequence information only. Second, we use the KLIFS pocket IFP (KLIFS IFP ) to probe if the KiSSim fingerprint, which does not contain any information about interactions, improves kinase similarity predictions compared to interaction-based fingerprints.