As early as 2006, Pedersen et al. performed MD simulations to study the interactions between cations and negatively charged lipid bilayers, and found that Ca 2+ ions exert a pronounced effect on bilayers by binding to anionic groups of lipid molecules. Later, further studies showed that the binding of Ca 2+ made the membrane bilayers more condensed, with decreasing APL, increasing thickness, and dehydration of the membrane interface. Notably, the speciic lipid composition and chemistry can also inluence these physical-chemical properties of membranes. Overall, the binding afinity between Ca 2+ ions and lipids was signiicantly stronger than that of Na + , 4 K + and Mg 2+ ions, regardless of the composition of the lipid bilayers. Meanwhile, we speculate that divalent cations such as Zn 2+ would produce similar results to Ca 2+ , while tri-valent ions may induce even stronger effects. Overall, our simulations obtained results consistent with the previous indings.