Because a single force field that would correctly reproduce the binding of all charged molecules to membranes is not yet available, we selected the best available models from this and our previous study to compare the binding of sodium, calcium, etidocaine and TPP to a POPC membrane. The density profiles, PMFs, and α-carbon order parameter decrease compared with experiments for these simulations are shown in Fig. . In these simulations, the sodium exhibits weaker binding affinity than other molecules as expected for simple monovalent ions. Calcium and TPP bind with similar affinities, while etidocaine exhibits the strongest binding. These relative binding affinities are in line with the experimentally determined number of bound particles in Fig. and measured order parameters, but not with the reported binding coefficients. Despite the similar binding affinities, TPP penetrates deeper in the membrane than calcium. This can be explained by a different binding mechanisms of these molecules. Calcium ions bind to phosphate oxygens in the POPC headgroup, whereas the binding of TPP is driven by the hydrophobic effect. Similarly to TPP, also etidocaine penetrates deeper into a membrane. The PMF profiles in Fig. show lower energy barrier at the membrane centre for etidocaine and TPP than for water, sodium and calcium.