The unambiguity in reported binding constants can be circumvented by directly comparing how lipid headgroup C-H bond order parameters change upon the addition of ions between simulations and experiments. These order parameters are proportional to the amount of charged molecules bound to the bilayer because binding of positive charges decreases their values (due to the orientation of the lipid headgroup dipole more parallel to the membrane normal) and vice versa for negative charges. As we are interested in the relative binding affinities between charged small molecules and biologically relevant simple ions, such as calcium and sodium, we use this approach here. From the available experimental data for headgroup order parameter changes upon binding of charged molecules, we chose to evaluate the binding affinities of etidocaine, tetraphenylphosphonium (TPP), dibucaine and cyclic somatostatin (SMS) binding to a POPC lipid bilayer in simulations.