In this study, we incorporated kinase phylogeny information through a detailed structural analysis conducted by Modi & Dunbrack . While we aimed to use the structureguided multiple sequence alignment to discern both intra-and inter-family relationships among kinases, our models did not show improved generalization to unseen kinase families. Nonetheless, generalization within kinase families was successful to some extent, suggesting that models might perform better within more closely related groups, however, broader kinome-wide predictions remain challenging. Overall, caution is advised when using sequential or structural embeddings in proteochemometric models.