AMBER Force Field Parameters for Cobalt-Containing Biological Systems: A Systematic Derivation Study

In the present work,
the parameterization of a set of cobalt-containing
systems has been performed to create a comprehensive library for bonding
parameters of biological Co-containing systems. A standard process
for the extraction and validation of parameters was employed, which
could be used to create force field parameters for the other metal-containing
systems. All protein data banks were searched to extract common chemical
groups in bonding with cobalt, and finally, 16 structures were designed
to represent the binding model of the chemical moieties with cobalt.
The Hessian matrix of each structure was computed at the B3LYP/6-311++G­(2d,2p)
level of theory and the Seminario method was employed to compute cobalt
bond stretching and angle bending parameters. Validation of the derived
parameters was performed using structural minimization and molecular
dynamics (MD) simulations of four models. Further validation was performed
using an extensive MD simulation on carbonic anhydrase II as a common
cobalt-containing metalloprotein. The results demonstrated that among
models, the bonded model in combination with the RESP charges can
produce the most reliable and accurate structural conformations for
the metal site of cobalt-containing systems.