A New Quantum Calibrated Force Field for Zinc-Protein Complex.

A quantum calibrated polarizable-charge transfer force field (QPCT) has been proposed to accurately describe the interaction dynamics of zinc-protein complexes. The parameters of the QPCT force field were calibrated by quantum chemistry calculation and capture the polarization and charge transfer effect. QPCTs are validated by molecular dynamic simulation of the hydration shell of the zinc ion, five proteins containing the most common zinc-binding sites (ZnCys2His2, ZnCys3His1, ZnCys4, Zn2Cys6), as well as protein-ligand binding energy in zinc protein MMP3. The calculated results show excellent agreement with the experimental measurement and with results from QM/MM simulation, demonstrating that QPCT is accurate enough to maintain the correct structural integrity of the zinc binding pocket and provide accurate interaction dynamics of the zinc-residue complex. The current approach can also be extended to the study of interaction dynamics of other metal-containing proteins by recalibrating the corresponding parameters to the specific complexes.