Developing Multisite Empirical Force Field Models for Pt(II) and Cisplatin

作者：Cvitkovic John P; Kaminski George A^*

来源：Journal of Computational Chemistry, 2017, 38(3): 161-168.

DOI：10.1002/jcc.24665

• Pt(II)
• cisplatin
• empirical force fields
• OPLSAA
• POSSIM
• polarizable force field

We have developed empirical force field parameters for Pt(II) and cisplatin. Two force field frameworks were used-modified OPLS-AA and our second-order polarizable POSSIM. A seven-site model was used for the Pt(II) ion. The goal was to create transferable parameter sets compatible with the force field models for proteins and general organic compounds. A number of properties of the Pt(II) ion and its coordination compounds have been considered, including geometries and energies of the complexes, hydration free energy, and radial distribution functions in water. Comparison has been made with experimental and quantum mechanical results. We have demonstrated that both versions are generally capable of reproducing key properties of the system, but the second-order polarizable POSSIM formalism permits more accurate quantitative results to be obtained. For example, the energy of formation of cisplatin as calculated with the modified OPLS-AA exhibited an error of 9.9%, while the POSSIM error for the same quantity was 6.2%. The produced parameter sets are transferable and suitable to be used in protein-metal binding simulations in which position or even coordination of the ion does not have to be constrained using preexisting knowledge.

• 出版日期2017-1