Voltage-dependent energetics of alamethicin monomers in the membrane

The implicit membrane model IMM1 is extended to include the effect of transmembrane potential and used to investigate the optimal membrane binding configurations and energies for alamethicin helices. In the absence of voltage, the lowest energy configuration is on the membrane surface with a tilt allowing the N terminus to be fully buried. Slightly higher in energy is an also tilted configuration with the N terminus deeper in the membrane and almost crossing the membrane. In 26 Å membranes and in the presence of 0.1 V voltage, the TM orientation becomes lower in energy. This is consistent with the assumption that voltage induces a transition from the interfacial to the inserted (TM) orientation. This effect of voltage is smaller in thicker membranes. The results are compared to previous experimental and theoretical studies and the findings are discussed in relation to the mechanism of channel formation by alamethicin.