Possible origins of mutational effects of L579F, L624P, and H606Q derived from the snapshots of various mutant simulations at 44 ns. The JH2 C-helix is shown in orange, the β-4 sheet in blue, and the β-5 sheet in red. In L579F, F579 interacts with nearby F628, changes the surrounding packing pattern, and causes conformational changes between the β-4 and β-5 sheets. In L624P, P624 enforces a conformational change of the β-5 sheet. In H606Q, the interactions between the H606 side chain and the L604/L609 backbones are disrupted and the conformation of the loop (604 to 609) is changed.