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

TL;DR

This study uses quantum mechanical calculations to analyze the electronic structure and dipole moment of charybdotoxin, revealing how its orbitals localize and how modifications can alter its electronic properties relevant to its function as a potassium channel blocker.

Contribution

First detailed localization of frontier orbitals in charybdotoxin and insights into how specific amino acid modifications affect its electronic structure.

Findings

HOMO localized on Trp14

LUMO localized on disulfide bonds

Trp14 to Ala14 substitution alters the HOMO-LUMO gap

Abstract

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-alpha-aminobutyric acid residues does not affect the H-L energy gap.