The talk will discuss our successful efforts in expanding the applicability of novel metal force-fields for accurate description of both thermodynamics and structural properties simultaneously. The 12−6−4 LJ-type nonbonded model that includes a 1/r⁴ term to incorporate charge-induced dipole interactions reproduces multiple experimental properties of highly charged metal ions.[1]-[3] We first optimized 12−6−4 LJ parameters for Cd²⁺, Ni²⁺, Fe²⁺, and Zn²⁺ binding to ethylenediamine (en) to capture the detailed structural and mechanistic insights of the chelate effect. [4] With these parameters we perform the first MD study exploring the structural details of chelate ring opening/closure. The study highlights the role of water molecules in the first solvation shell of the metal ion in facilitating the chelate ring formation.

We next modeled the thermodynamics of a transition metal (TM) ion assembly in proteins. We studied Glyoxalase I to obtain accurate structural and absolute binding free energies of Co²⁺ and Ni²⁺ to the protein using an optimized 12−6−4 (m12−6−4) potential.⁵ Critically, this model simultaneously reproduces the solvation free energy of the individual TM ions and reproduces the thermodynamics of TM ion−ligand coordination as well as the thermodynamics of TM ion binding to a protein active site unlike extant models.
The success of these models led us to develop 12-6-4 LJ non-bonded models for monovalent metal ions with OPC, OPC3 and TIP3P-FB water models.⁶ These new parameters further improve the accuracy of description of metal-water interactions and are suitable for simulations for metalloproteins in aqueous environment.

Zhen Li

Appearances