Binding affinities and stoichiometries of Na+ and Ca2+ ions to phospholipid bilayers are
of paramount significance in the properties and functionality of cellular membranes. Current
estimates of binding affinities and stoichiometries of cations are, however, inconsistent
due to limitations in the available experimental and computational methods. In this work, we
improve the description of the binding details of Na+ and Ca2+ ions to the 1-Palmitoyl-2-
oleoyl-phosphatidylcholine (POPC) bilayer by implicitly including electronic polarization as
a mean field correction, known as the electronic continuum correction (ECC). This is applied
by scaling the partial charges of a selected state-of-the-art POPC lipid model for molecular
dynamics simulations. Our improved ECC-POPC model reproduces not only the experimentally
measured structural parameters for the ion-free membrane, but also the response of lipid
head group to a strongly bound cationic amphiphile, as well as the binding affinities of Na+
and Ca2+ ions. With our new model we observe on the one side negligible binding of Na+
ions to POPC bilayer, while on the other side stronger interactions of Ca2+ primarily with
phosphate oxygens, which is in agreement with the previous interpretations of the experimental
spectroscopic data. The present model results in Ca2+ ions forming complexes with one
to three POPC molecules with almost equal probabilities, suggesting more complex binding
stoichiometries than those from simple models used to interpret the NMR data previously. The
results of this work pave the way to quantitative molecular simulations with realistic electrostatic
interactions of complex biochemical systems at cellular membranes.