Development of a Fluctuating Charge Model for Zinc Containing Metalloproteins

The fluctuating charge (FQ) model can generate atomic charges much more efficiently than quantum mechanical methods. The FQ model has been developed for a wide range of applications, but few models were specifically tailored for calculating atomic charges of metalloproteins. Zinc-containing proteins widely exist in biology and play important roles in various processes. In this study, we present a fluctuating charge model for zinc-containing metalloproteins based on the charge equilibration (Qeq) scheme. Our model was parameterized to reproduce CM5 charges, which demonstrated excellent performance in reproducing molecular dipole moments. During our study, we found that adding the Pauling-bond-order-like term (referred to as the "+C term" in a previous study) between the zinc ion and ligating atoms significantly improves the model's performance. Although our model was trained for four-coordinated zinc sites only, our tests indicated it can well describe the atomic charges in five- and six-coordinated zinc sites as well. Finally, we adapted our model to generate partial charges for the metal site in a zinc finger domain. These charges exhibited comparable performance to the widely used restrained electrostatic potential (RESP) charges in molecular dynamics (MD) simulations. The current model can be extended to other metal-containing systems and serve the molecular modeling community.