Mechanisms and dynamics of peptide permeation across membranes probed by molecular simulations

Cell-penetrating peptides (CPPs) are capable of delivering drug cargos across cell membranes. The mechanism of this transport is, however, still unclear. Here we use molecular dynamics simulations and potential of mean force calculations to identify the molecular mechanism involved in CPP permeation across membranes. Specifically, we aim to clarify the energetics involved in two debated CPP pathways, namely direct membrane translocation and CPP leakage during membrane fusion