Insights into Translocation of Arginine-Rich Cell-Penetrating\nPeptides across a Model Membrane

It\nis well-known that membrane deformation and water pores contribute\nto the spontaneous translocation of arginine-rich cell-penetrating\npeptides (CPPs). We confirm this through the observation of the spontaneous\ntranslocation of single R9 (nona-arginine) and Tat (48–60)\npeptides across a model membrane using the weighted ensemble (WE)\nmethod within all-atom molecular dynamics (MD) simulations. Furthermore,\nwe demonstrate that membrane deformation and the presence of a water\npore reduce the effective charge of the CPP and the bending rigidity\nof the model membrane during translocation. We find that R9 disturbs\nthe model membrane more than Tat (48–60), leading to more efficient\ntranslocation of R9 across the model membrane.