Figure : a) Molecule number density profiles and PMF profile from simulations giving the most realistic binding affinities of etidocaine (CHARMM36-ParamChem), TPP (CHARMM36-ProteinFF), calcium and sodium (simulations with ECC correction 47 ) according to the headgroup order parameters responses. Results from CHARMM36 with ECC applied are shown for calcium and sodium, 70,74 but simulation with ECC applied to Amber parameters would give essentially the same conclusions. 18 b) Experimental NMR α-carbon order parameter responses to etidocaine, TPP, calcium and sodium ions are shown as full lines together with selected most realistic simulations shown as dash lines.