Table 2.

Energetics of the Inhibition of Shaw-Related K⁺ Channels by 1-Butanol and the α-Helical Propensity of the S4–S5 Loop

K+ channel	Kia (mM)	ΔGBb (kcal/mol)	ΔΔGBc (kcal/mol)	ΔGHd (kcal/mol)	ΔΔGHe (kcal/mol)
Shaw2	17	−2.40	0	8.5	0
Kv3.4	70	−1.57	0	10.7	0
Shaw2-SK	63	−1.63	−0.77	11.7	−3.2
Kv3.4-G371I	39	−1.91	0.35	9	1.7
Kv3.4-KS	10	−2.71	1.14	7.4	3.3

^aApparent equilibrium dissociation constants obtained from 1-butanol dose–inhibition curves as described previously (17, 18).

^bGibbs free energy changes for 1-butanol inhibition (ΔG = RT ln K_i, where R and T are the universal gas constant and the absolute temperature, respectively).

^cDifference between binding free energy changes of the mutants relative to that of the wild type (ΔΔG_B = ΔG_BWT − ΔG_BMUT).

^dTheoretical Gibbs free energy changes of the helix–coil equilibrium in the S4–S5 loop (Materials and Methods).

^eDifference between the calculated helix–coil free energy changes of the mutants relative to that of the wild type (ΔΔG_H = ΔG_HWT − ΔG_HMUT).