Work Package 1

Besançon, France, Apr 2016

WP2: QM computations of the drugs and development of MD force fields

Objectives: Parametrization of drugs containing metallic species (Au,Pt)

QM --> QD --> FF

  • Task 1: QM optimization of drugs to obtain optimal geometry in vacuum and in water.
  • Task 2: QD simulations to estimate the fluctuations of atoms.
  • Task 3: Fitting procedure to determine the empirical force field of the drugs on the basis of the data of QM and QD calculations.
  • Drugs: anticancer drugs mainly including Pt derived drugs like cisplatin, carboplatin, oxaliplatin and Au derived like Auranofin

Secondments

UFC->UFJF for training in QM and sharing our QD expertise.

IP->UFJF for training in QM and sharing MD expertise.

IP->UFC (invited fellowship at UFC, funded separately by UFC) for sharing methods to deriving empirical force field.

WP2 tasks: QM computations of the drugs and developments of MD force fields

WP2: Future Implementations and links between WP3 and WP4: Into the cisplatin/cell machinery and cell resistance to Pt drugs

  • WP2 FI-1: kinetics of cisplatin within different solvent (M. Savenko, Ukraine ): completed
  • WP2 FI-2: binding to thiol riched metallothioneins and chelation with glutathions (T. Minervini, France) In progress
  • WP2 FI-3: kinetics/uptake of cisplatin : link between WP2 and WP3 and WP5 (T. Rivel, France) In Progress

WP2: Dissemination

Dissemination of Scientific Results

  1. “Empirical force field for cisplatin based on quantum dynamics data: case study of new parameterization scheme for coordination compounds”, Journal of molecular modeling 21 (10), 268.
  2. “Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery”, Nature Communications, 2017, DOI: 10.1038/ncomms15678 (also accounts for WP3).
  3. Report about Nature Communications paper on the web site of NAS of Ukraine http://www.nas.gov.ua/UA/Messages/News/Pages/View.aspx?MessageID=3232
  4. Report about Nature Communications paper in the “Health of Ukraine” journal.
  5. Report about Nature Communications paper on the web site of Chrono-Environnement laboratory France https://chrono-environnement.univ-fcomte.fr/spip.php?article2575
  6. Report about Nature Communications paper in the “JDD” French National journal http://www.lejdd.fr/societe/sciences/des-nanomedicaments-pour-soigner-les-cancer-3358973

Connected Activities

• Report and news of the secondment published on our Lab’s websites

• 3 invited oral presentions on “Infodays” organized by International board at UFC for potential new participants to H2020 research actions.

• Participation at the “night for researchers” september 2017 in Besançon.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 690853