Translocation of a single Arg9 peptide across a DOPC/DOPG(4:1) model membrane using the weighted ensemble method

Abstract

A spontaneous translocation of cell-penetrating peptides(CPPs) in all-atom molecular dynamics(MD) simulations is not expected within a short time scale (e.g., a few hundred ns) because it is believed that the time required for the translocation of usual CPPs is on the order of minutes. In this study, we report a single Arg9(R9) peptide translocation across a DOPC/DOPG(4:1) model membrane within an order of a few tens ns scale by using the weighted ensemble(WE) method, one of the most powerful and flexible path sampling techniques. We present free energy profiles of the translocation across the membrane and identify how water molecules play a role during the translocation. We also show how the orientation of Arg9 affects the translocation and how lipid molecules were transported along with Arg9. Our approach can help study interactions of CPPs with various model membranes within MD simulation approaches.