Differential impacts of R-to-Q mutations in VSD _I and VSD _II during up-to-down transitions. (A and B) The differential dynamic behaviors of R-to-Q mutations (R1, R2, and R3) in VSD_I (A) and VSD_II (B) in comparison to the WT under an external electric field of −500 mV. Traces of z positions for Cα atoms of the gating-charge residues in S4 relative to that of the HCS are shown in each panel to track the structural changes. Molecular images of VSDs are presented in a white cartoon representation, illustrating the initial and final frames with licorice representations of gating charges (blue), countercharges (red), and the HCS (green). Only one representative trajectory among three independent runs for each mutant is illustrated here.