Monte Carlo-energy minimization of correolide in the Kv1.3 channel: possible role of potassium ion in ligand-receptor interactions

Table 2 Correolide-sensing residues in the inner helices^a and their energy contributions ^b (kcal/mol) to correolide binding

	K+-chelating groups of correolide
	Model 2/4		Model 1/3/5
	Epoxy	Ether^c	Epoxy	Ether^c	Acetoxy^d
Inner-helix mutations affecting correolide binding ^a
Ala⁴¹³Cys
Val⁴¹⁷Ala	-2.6	-3.1	-2.3	-2.6	-2.5
Leu⁴¹⁸Ala	-1.4	-0.9	-1.8	-1.9	-1.7
Thr⁴¹⁹Ala			-0.6	-0.4
Ala⁴²¹Cys	-4.2	-2.5	-1.8	-5.0	-2.0
Leu⁴²²Ala	-0.9	-0.4	1.2	-2.1	-0.6
Pro⁴²³Ala		-1.0		-1.2
Val⁴²⁴Ala	-2.2	-4.7	-4.2	-2.8	-4.5
Pro⁴²⁵Ala	-1.0	-4.4	-3.7	-1.7
Mutation affecting channel expression ^e
Ile⁴²⁰Ala	-5.1	-1.3	-0.6	-0.8	-1.8
Predicted ligand-receptor energy	-20.6	-20.3	-19.1	-22.4	-21.9

^a Mutations that change correolide binding energy by more than 1 kcal/mol [15].
^b Energy contribution of a residue was summed over four domains. Contributions with the absolute energy less than 0.4 kcal/mol are not shown.
^c Ether group in the seven-membered ring.
^d Three acetoxy groups (Fig. 4E).
^e Ile⁴²⁰ contributes to correolide binding in our models, but is not categorized as a correolide-sensing residue because its mutation results in poor expression of the channels [15].

ISSN: 1472-6807