Mechanism of water transport through the lipid membrane with trichogin GA IV. Molecular dynamics study

We perform all-atom molecular dynamics simulations of the antimicrobial peptide trichogin GA IV (TG) inside a model DOPC lipid membrane to clarify the mechanism of water transport increase. We considered the behavior of individual TG molecules inside the membrane as well as their aggregates: dimers, tetramers, and octamers. Our calculations show that a TG molecule moves into the membrane from the surrounding water and is localized in the lipid heads region. In this case, TG does not promote the permeation of water molecules through the membrane. The penetration of water into the hydrophobic region of the membrane occurred along the TG molecules that have formed transmembrane clusters (starting from dimers). In this case, the water molecules moved along the peptides by thermally induced hydrogen bond hopping allowing them to pass through the membrane. We show that the transmembrane clusters formed from non-helical TG molecules are more stable and provide increased permeability, since they can form additional hydrogen bonds, both with each other and with water, compared to the helical ones. We note that all considered TG clusters are compact and embedded in the membrane. They do not lead to a noticeable disruption of the membrane structure in their environment, and there are no pores or channels for the movement of water molecules, even in the case of an octamer. The movement of water molecules along all clusters occurs exclusively due to the hydrogen bond hopping mechanism.