In conclusion, our results indicate that the binding affinities of charged drugs, etidocaine, dibucaine and SMS, are significantly stronger to zwitterionic membranes than the binding affinities of sodium and calcium. Also, their binding mechanisms differ from that of monoatomic ions. Therefore, the binding of these drugs to membranes would be most likely not interfered by physiological ions. On the other hand, the binding of TPP could be interfered by calcium as their affinities are similar, yet their interrelated binding may be complicated as their binding mechanisms are different. MD simulations have the potential to model such complex behaviour, but force field parameters correctly capturing both TPP and calciumbinding are not yet available. Furthermore, improvements in force fields would be needed to correctly model the binding of etidocaine to POPC headgroups as the experimental response of β-carbon order parameters to the number of bound molecules is not captured by any simulation models in Fig. .