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
based on classical force fields has emerged as an important tool in
scientific research. Partial charges are critical parameters within
classical force fields and usually derived from quantum mechanical
(QM) calculations. However, QM calculations are often time-consuming
and prone to basis set dependence. Alternatively, fluctuating charge
(FQ) models offer another avenue for partial charge derivation, which
has significant speed advantages and can be used for large-scale
screening. Building upon our previous work, which introduced an FQ
model for zinc-containing complexes, herein we extend this model to
include additional 3d transition metals which are important to the
life sciences, namely chromium, manganese, iron, cobalt, and nickel.
Employing CM5 charges as target for parametrization, 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. These
charges showed excellent performance in simulating proteomic metal
sites housing multiple metal ions, specifically, a metalloprotein
containing an iron–sulfur cluster and another containing a
dimanganese metal site, showcasing comparable performance to those
of RESP charges. We anticipate that our study can accelerate the parametrization
of atomic charges for metalloproteins featuring 3d transition metals,
thereby facilitating simulations of relevant systems.