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 (MMP2-) is strongly influenced by the types and combinations of cations in the aqueous solution. Although Ca2+ promotes the formation of stable and large MMP2- 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 MMP2- clustering effect of Ca2+ in the presence of K+ is confirmed by Fourier transform infrared spectroscopy. The characterization of the cation-dependent clustering of MMP2- provides a starting point for understanding cation-dependent clustering of phosphoinositides in cell membranes.