Abstract
It is difficult to observe a spontaneous translocation of cell-penetrating peptides(CPPs) within a short time scale (e.g., a few hundred ns) in all-atom molecular dynamics(MD) simulations because the time required for the translocation of usual CPPs is on the order of minutes or so. In this work, we report a spontaneous translocation of a single Arg[Formula: see text](R9) across a DOPC/DOPG(4:1) model membrane within an order of a few tens ns scale by using the weighted ensemble(WE) method. We identify how water molecules and the orientation of Arg[Formula: see text] play a role in translocation. We also show how lipid molecules are transported along with Arg[Formula: see text]. In addition, we present free energy profiles of the translocation across the membrane using umbrella sampling and show that a single Arg[Formula: see text] translocation is energetically unfavorable. We expect that the WE method can help study interactions of CPPs with various model membranes within MD simulation approaches.