JAK2 activation mechanism.Trans phosphorylation of JAK2 TK (purple) domain. Stability analysis of the TK-TK interface, measured by the distance between the center of mass of Cα atoms within residues (849-1124) in both JAK2 TK domains. The right panel displays the activation loop of 1 TK domain penetrating the nucleotide-binding pocket of the adjacent TK domain, elucidating the mechanism of JAK2 activation. The solid line on the graph shows the exponential moving average over the course of a 1.3-μs MD simulation.