Translocation of a single Arg 9 peptide across a DOPC/DOPG(4:1) model membrane using the weighted ensemble method

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 Arg9(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 Arg9 play a role in translocation. We also show how lipid molecules are transported along with Arg9. In addition, we present free energy profiles of the translocation across the membrane using umbrella sampling and show that a single Arg9 translocation is energetically unfavorable. We expect that the WE method can help study interactions of CPPs with various model membranes within MD simulation approaches. © 2023, The Author(s).