title: Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds.
abstract: Parameterization of molecular complexes containing a metallic compound, such as cisplatin, is challenging due to the unconventional coordination nature of the bonds which involve platinum atoms. In this work, we develop a new methodology of parameterization for such compounds based on quantum dynamics (QD) calculations. We show that the coordination bonds and angles are more flexible than in normal covalent compounds. The influence of explicit solvent is also shown to be crucial to determine the flexibility of cisplatin in quantum dynamics simulations. Two empirical topologies of cisplatin were produced by fitting its atomic fluctuations against QD in vacuum and QD with explicit first solvation shell of water molecules respectively. A third topology built in a standard way from the static optimized structure was used for comparison. The later one leads to an excessively rigid molecule and exhibits much smaller fluctuations of the bonds and angles than QD reveals. It is shown that accounting for the high flexibility of cisplatin molecule is needed for adequate description of its first hydration shell. MD simulations with flexible QD-based topology also reveal a significant decrease of the barrier of passive diffusion of cisplatin accross the model lipid bilayer. These results confirm that flexibility of organometallic compounds is an important feature to be considered in classical molecular dynamics topologies. Proposed methodology based on QD simulations provides a systematic way of building such topologies.
authors.affiliation: Department of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Prospect Nauky 46, Kiev-28, 03680, Ukraine.
authors.forename: S
authors.initials: S
authors.lastname: Yesylevskyy
authors.affiliation: Laboratoire Chrono Environnement UMR CNRS 6249, Université de Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cardey
authors.affiliation: Department of Biomedical Engineering (W11/K7), Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370, Wroclaw, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Kraszewski
authors.affiliation: Laboratoire Chrono Environnement UMR CNRS 6249, Université de Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Foley
authors.affiliation: Laboratoire Chrono Environnement UMR CNRS 6249, Université de Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France.
authors.forename: Mironel
authors.initials: M
authors.lastname: Enescu
authors.affiliation: Núcleo de Estudos em Química Computacional, Departamento de Química, ICE, Universidade Federal de Juiz de Fora (UFJF), Campus Universitário, Martelos, Juiz de Fora, MG, 36036-900, Brazil.
authors.forename: Antônio M
authors.initials: AM
authors.lastname: da Silva
authors.affiliation: Núcleo de Estudos em Química Computacional, Departamento de Química, ICE, Universidade Federal de Juiz de Fora (UFJF), Campus Universitário, Martelos, Juiz de Fora, MG, 36036-900, Brazil.
authors.forename: Hélio F
authors.initials: HF
authors.lastname: Dos Santos
authors.affiliation: Laboratoire Chrono Environnement UMR CNRS 6249, Université de Franche-Comté, 16 route de Gray, 25030, Besançon Cedex, France. christophe.ramseyer@univ-fcomte.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ramseyer
keywords: Cisplatin; Coordination compounds; Molecular dynamics; Parameterixation; Quantum dynamics