The local electric field response R (left) and the system’s response propensity ζ^j (right) estimated for 10 different membrane proteins. They include voltage-gated potassium channel Shaker (Long et al., 2007; Yazdi et al., 2016), voltage-gated sodium channel NavMs (Sula et al., 2017), Cx26 (Maeda et al., 2009), TRPV1 (Cao et al., 2013; Liao et al., 2013; Kasimova et al., 2018), VDAC1 (Ujwal et al., 2008), ClC1 (Park and MacKinnon, 2018), muscarinic acetylcholine receptor M₂ (Haga et al., 2012), Na⁺/K⁺ ATPase (Kanai et al., 2013), GLIC (Sauguet et al., 2014), and two-pore domain potassium channel TWIK-1 (Miller and Long, 2012). The slices of the systems along the normal to the membrane are shown. The gray area shows the regions that are not accessible to water (i.e., the proteins and the membrane). To clearly represent $ζ j$⁠, we approximated each point charge of the system element j with a Gaussian distribution (σ = 1.5 Å) and then integrated the signal over 25 slices (each 1 Å wide) parallel to the plane shown in the figure. Only the values above the detection threshold were considered for the integration (see Materials and methods). Shaker, NavMs, Cx26, VDAC1, and ClC1, for which changes in the MP are the primary stimulus for activation, have the largest $ζ j$values, while TRPV1, which is known to be very weakly voltage-sensitive (Caterina et al., 1997; Nilius et al., 2005; Boukalova et al., 2010), has the smallest $ζ j$ value among the voltage-sensitive membrane proteins.