Graph-Theoretic Analysis of Monomethyl Phosphate Clustering in Ionic Solutions

All-atom molecular dynamics simulations combined with graph-theoretic analysis reveal that clustering of monomethyl phosphate dianion (MMP^2-) is strongly influenced by the types and combinations of cations in the aqueous solution. Although Ca²⁺ promotes the formation of stable and large MMP^2- clusters, K⁺ alone does not. Nonetheless, clusters are larger and their link lifetimes are longer in mixtures of K⁺ and Ca²⁺. This "synergistic" effect depends sensitively on the Lennard-Jones interaction parameters between Ca²⁺ and the phosphorus oxygen and correlates with the hydration of the clusters. The pronounced MMP^2- clustering effect of Ca²⁺ in the presence of K⁺ is confirmed by Fourier transform infrared spectroscopy. The characterization of the cation-dependent clustering of MMP^2- provides a starting point for understanding cation-dependent clustering of phosphoinositides in cell membranes.