Molecular dynamics simulation of the Pb(II) coordination in biological media via cationic dummy atom models

The coordination of Pb(II) in aqueous solutions containing thiols is a pivotal topic to the understanding of the pollutant potential of this cation. Based on its hard/soft borderline nature, Pb(II) forms stable hydrated ions as well as stable complexes with the thiol groups of proteins. In this paper, the modeling of Pb(II) coordination via classical molecular dynamics simulations was investigated to assess the possible use of non-bonded potentials for the description of the metal-ligand interaction. In particular, this study aimed at testing the capability of cationic dummy atom schemes-in which part of the mass and charge of the Pb(II) is fractioned in three or four sites anchored to the metal center-in reproducing the correct coordination geometry and, also, in describing the hard/soft borderline character of this cation. Preliminary DFT calculations were used to design two topological schemes, PB3 and PB4, that were subsequently implemented in the Amber force field and employed in molecular dynamics simulation of either pure water or thiol/thiolate-containing aqueous solutions. The PB3 scheme was then tested to model the binding of Pb(II) to the lead-sensing protein pbrR. The potential use of CDA topological schemes in the modeling of Pb(II) coordination was here critically discussed.