Motions of the activation loop and αC-helix in JAK2-WT and JAK2-V617F in 30 ns MD simulation.

<p>(A) The JAK2-V617F mutant increases the flexibility of the activation loop in the kinase domain by restricting the movement of αC helix region in the JH2. The activation loop in the kinase domain of JAK2-WT (black) and JAK2-V617F (red) is shown alongside the crystal structure (green) in cartoon representation using PyMOL. Other residues are shown in surface representation. (B) RMSDs of Cα atoms during 30 ns of MD simulation show displacement of the kinase domain activation loop residues 994–1028 in the V617F mutant (black) but not the wildtpype (red). (C) Conformations of the αC helix in kinase domain after 30 ns MD for V617F mutant (black) and wild type (red). (D) RMSDs for the kinase αC helix (residues 586–606) in JAK2-WT and JAK2-V617F during 30 ns MD simulation show that the position of this helix is relatively stable in both cases. RMSDs are computed over Cα atoms of JAK2 with respect to the initial model after superposition of the kinase domain.