The density distributions along the membrane normal were calculated using a histogram method. Atom coordinates were centred around the centre of mass of the POPC lipid molecules for every time frame, and a histogram of these centred positions was calculated with the bin width of 1/3 Å. The script utilizing MDAnalysis module in Python is available at . Potential of mean force (PMF) profiles were calculated from the density profiles ρ(z) using the inverse Boltzmann formula PMF = -k b T ln ρ(z). When calculating the number of contacts to specific regions (such as phosphate group), two atoms were considered to be in contact when the distance between them was smaller than 0.325 nm. Permeation of particles through the membrane bilayer was analysed by the program from Camilo at al. Instead of water oxygen used in the original work, the N14 atom was used for the analysis of permeation of etidocaine and the P atom was used for TPP molecules.