Mutations in the human leucine rich repeat protein kinase-2(LRRK2)create risk factors for Parkinson’s disease, and pathologicalfunctions of LRRK2 are often correlated with aberrant kinase activity.Past research has focused on developing selective LRRK2 kinase inhibitors.In this study, we combined enhanced sampling simulations with HDX-MSto characterize the inhibitor-induced dynamic changes and the allostericcommunications within the C-terminal domains of LRRK2, LRRK2RCKW. Here, LRRK2 is linked to Parkinson disease.