In this work, we study the dynamics and the energetics of the all-atom structure of a neuronal-specific serine/threonine kinase c-Jun N-terminal kinase 3 (JNK3) in three states: unphosphorylated, phosphorylated, and ATP-bound phosphorylated. A series of 2 µs atomistic simulations followed by a conformational landscape mapping and a principal component analysis supports the mechanistic understanding of the JNK3 inactivation/activation process and also indicates key structural intermediates. Our analysis reveals that the unphosphorylated JNK3 undergoes the 'open-to-closed' movement via a two-step mechanism. Furthermore, the phosphorylation and ATP-binding allow the JNK3 kinase to attain a fully active conformation. JNK3 is a widely studied target for small-drugs used to treat a variety of neurological disorders. We believe that the mechanistic understanding of the large-conformational changes upon the activation of JNK3 will aid the development of novel targeted therapeutics.