Melittin can permeabilize membranes via large transient pores
Jakob P. Ulmschneider, Martin B. Ulmschneider
Abstract
Membrane active peptides are known to porate lipid bilayers, but their exact permeabilization mechanism and the structure of the nanoaggregates they form in membranes have often been difficult to determine experimentally. For many sequences at lower peptide concentrations, transient leakage is observed in experiments, suggesting the existence of transient pores. For two well-know peptides, alamethicin and melittin, we show here that molecular mechanics simulations i) can directly distinguish equilibrium poration and non-equilibrium transient leakage processes, and ii) can be used to observe the detailed pore structures and mechanism of permeabilization in both cases. Our results are in very high agreement with numerous experimental evidence for these two peptides. This suggests that molecular simulations can capture key membrane poration phenomena directly and in the future may develop to be a useful tool that can assist experimental peptide design. Many membrane active peptides perforate lipid bilayers. Alamethicin and melittin, two well known examples. Here the authors show that atomic detail simulations can distinguish between equilibrium and transient leakage processes, and predict the detailed pore structures and mechanism of perforation.