The electronic structure and dipole moment of charybdotoxin, a scorpion venom peptide with K+ channel blocking activity

The electronic structure of charybdotoxin (ChTX), a scorpion venom peptide that is known to act as a potassium channel blocker, is investigated with the aid of quantum mechanical calculations. The dipole moment vector (=145 D) of ChTX can be stirred by the full length KcsA potassium channel’s macrodipole (=403 D) thereby assuming the proper orientation before binding the ion channel on the cell surface. The localization of the frontier orbitals of ChTX has been revealed for the first time. HOMO is localized on Trp14 while the three lowest-energy MOs (LUMO, LUMO+1, and LUMO+2) are localized on the three disulfide bonds that characterize this pepetide. An effective way to engineer the HOMO-LUMO (H-L) gap of ChTX is that of replacing its Trp14 residue with Ala14 whereas deletion of the LUMO-associated disulfide bond with the insertion of a pair of L--aminobutyric acid residues does not affect the H-L energy gap.