Nevertheless, we consider that the responses of the α-carbon order parameters are sufficiently close to experiments to be used for the validation of etidocaine and TPP binding affinities in simulations, yet the observed inaccuracy should be taken into account when interpreting the results. The decrease in the α-carbon order parameter as a function of eti-docaine concentration in water in Fig. ) correlates with the binding affinity in Fig. ing which is then overestimated after applying the ECC. However, because QM-derived partial charges are presumably more realistic, the better results with CHARMM36-ProteinFF parameters probably originate from the cancellation of errors.