PAbstract: The potential of protein kinases as drug targets for a wide range of diseases is now well established. However, targeting kinases directly through competitive inhibitors poses a major selectivity challenge, as kinase active sites are typically quite conserved. A promising alternative strategy to inhibit kinases with enhanced selectivity relies on allosteric modulation. Allosteric sites are often subject to lower evolutionary pressure compared to active sites and therefore are less conserved across the kinase superfamily. However, it is not fully understood how kinases integrate multiple concurrent allosteric signals and how the dynamics underlying allosteric regulation influence the potencies and efficacies of allosteric drug leads. We will present our attempts to answer these fundamental questions for prototypical kinases, such as the mammalian Protein Kinase A (PKA) or the Plasmodium falciparum Protein Kinase G (PKG), using a combination of NMR spectroscopy, simulations as well as enzymatic and binding assays