Accurate Metal-Imidazole Interactions

Modeling the interaction between a metal ion and small molecules can provide pivotal information to bridge and close the gap between two types of simulations: metal ions in water and metal ions in metalloproteins. As previously established, the 12-6-4 Lennard-Jones (LJ)-type nonbonded model, because of its ability to account for the induced dipole effect, has been highly successful in simulating metal ion systems. Using the potential of mean force (PMF) method, the polarizability of the metal-chelating nitrogen from two types of imidazole molecules, delta nitrogen protonated (HID) and epsilon nitrogen protonated (HIE), has been parametrized against experiment for 11 metals (Ag(I), Ca(II), Cd(II), Co(II), Cu(I), Cu(II), Fe(II), Mg(II), Mn(II), Ni(II), and Zn(II)) in conjunction with three commonly used water models (TIP3P, SPC/E, and OPC). We show that the standard 12-6 and unmodified 12-6-4 models are not able to accurately model these interactions and, indeed, predict that the complex should be unstable. The resultant parameters further establish the flexibility and the reliability of the 12-6-4 LJ-type nonbonded model, which can correctly describe three-component interactions between a metal, ligand, and solvent by simply tuning the polarizability of the chelating atom. Also, the transferability of this model was tested, showing the capability of describing metal-ligand interactions in various environments.