Parameterization of a Fluctuating Charge Model for Complexes Containing 3d Transition Metals

Metalloproteins widely exist in biology, playing pivotal roles in diverse life processes. Meanwhile, molecular dynamics (MD) simulations, which are driven by classical force fields, have emerged as indispensable tools in scientific research. Among the critical parameters within classical force fields are partial charges, which are traditionally derived from quantum mechanical (QM) calculations. However, QM calculations are often time-insensitive and prone to basis set dependence. Alternatively, fluctuating charge (FQ) models offer a promising avenue for partial charge derivation, boasting significant speed advantages conducive to large-scale screening. Building upon our previous work, which tailored an FQ model for zinc-containing complexes, we have extended this model to include additional 3d transition metals integral to the life sciences, namely chromium, manganese, iron, cobalt, and nickel. Employing CM5 charges as reference points for parameterization, our FQ model accurately reproduces partial charges for 3d metal complexes featuring biologically relevant ligands. Furthermore, by using atomic charges derived by our FQ model, MD simulations have been performed, and the results show excellent performance in simulating proteomic metal sites housing multiple metal ions. Specifically, our simulations accurately capture the behavior of a metalloprotein containing an iron-sulfur cluster and another containing a di-manganese metal site. These results showcase comparable performance to those of RESP charges. We anticipate that our study can accelerate the parameterization of atomic charges, thereby facilitating simulations of metalloproteins featuring 3d transition metals.