Institut Lumière Matière UMR 5306/UCBL : Claire Loison
Institut de Biologie Structurale UMR 5075/CEA/UJF : Jérôme Boisbouvier
Formation M2 : Elisa Rioual
Centre Blaise Pascal : Emmanuel Quémener

Proteins are not frozen : their conformation evolve in time, for instance after the interaction with a ligand, or during a catalytic cycle. Conformational dynamics of protein may even become essential to biological phenomena, such as the recognition of physiological partners. Nevertheless, rational Drug Design rarely consider these conformational plasticity. Nuclear Magnetic Resonance (NMR), and molecular dynamics simulation are complementary techniques which provide information on protein dynamics at various timescales (ns, ps, ms). The objective of the Dyn4Drugs project is to bring new tools, based on liquid NMR spectroscopy, to improve the success of rational Drug Design by incorporating in the protocol a better knowledge of protein conformational dynamics.

The N-terminal part of the Heat-Shock-Protein-90 (NT-HSP90), already well known of the experimental group, is the model of this study. This chaperone is considered as a potential therapeutic target: some of its inhibitors can be potential and effective cancer chemotherapeutic drugs and have been examined in clinical trials. Depending on its interaction with various ligand, this protein changes its dynamics (see Fig.(a)). The objective of the project is to gather knowledge on the protein dynamics using state-of-art NMR relaxation measurements associated to molecular modeling. The experimental step takes place in IBS (Grenoble) and consists of the study of NT-HSP90 dynamics. Spin nuclear relaxation measurement will be performed on samples synthesized in the group and ligands ontained by collaborations. The experimental data, after analysis, will be integrated into the molecular modeling step. This projet is supported by the AURA region (Pack Ambition Recherche DYN4DRUGS).

Contribution du CBP

The Centre Blaise Pascal provides :

  • support for the analysis of the NMR experimental data (eNORA matlab library)
  • expertise in molecular dynamics applications
recherche/projets/dyn4drugs2020.txt · Dernière modification: 2020/04/12 20:22 par equemene