Voltage-dependent insertion of alamethicin at phospholipid/water and octane/water interfaces

Understanding the binding and insertion of peptides in lipid bilayers is a prerequisite for understanding phenomena such as antimicrobial activity and membrane-protein folding. We describe molecular dynamics simulations of th e antimicrobial peptide alamethicin in lipid/water and octane/water environ ments, taking into account an external electric field to mimic the membrane potential. At cis-positive potentials, alamethicin does not insert into a phospholipid bilayer in 10 ns of simulation, due to the slow dynamics of th e peptide and lipids. However, in octane N-terminal insertion occurs at fie ld strengths from 0.33 V/nm and higher, in simulations of up to 100 ns dura tion. Insertion of alamethicin occurs in two steps, corresponding to desolv ation of the Gln7 side chain, and the backbone of Aib10 and Gly11, The prol ine induced helix kink angle does not change significantly during insertion . Polyalanine and alamethicin form stable helices both when inserted in oct ane and at the water/octane interface, where they partition in the same loc ation. In water, both polyalanine and alamethicin partially unfold in multi ple simulations. We present a detailed analysis of the insertion of alameth icin into the octane slab and the influence of the external field on the pe ptide structure. Our findings give new insight into the mechanism of channe l formation by alamethicin and the structure and dynamics of membrane-assoc iated helices.