Kinases are a class of enzymes that play a crucial role in various biochemical processes and are a prototypical example of enzymes that use signalling cascades and conformational gated chemical reactions. In project P5, we investigate histidine kinases as a model system to gain a more comprehensive understanding of these processes. The conformational transition of a histidine kinase leads to the autophosphorylation of a conserved histidine residue through a catalytic process. To study this chemical step, we perform QM/MM simulations that employ DFTB as a quantum mechanical method to simulate the process on a time scale of up to a microsecond. In the future, we want to broaden our spectrum to study the conformational transition in different enzymes and develop a multiscale methodology that is able to switch between coarse-grained and all-atom MD simulations.