CaMKII conformational coupling

CaMKII is a multi-subunit kinase, activated by calcium calmodulin upon calcium jumps produced by synaptic stimulation. After return to basal calcium levels, the kinase can remain activated and mediate long-term behavioural effect through auto-transphosphorylation of a regulatory peptide. We have developed a computational model of the conformational plasticity of the kinase domain by combination of molecular simulations and network analysis. The location of known pathological mutations is in agreement with model. This novel understating of the molecular details of CaMKII activation reveals target sites for drug development.