In Silico Studies

Deepen cytokine / receptor interaction by in silico Studies.

  Technical and scientific manager: Agnès Quéméner Materials: Discovery Studio software (Dassault Systèmes BIOVIA)


Cytokine / Receptor interactions study


Comparison of the binding of IL-2, IL-4 and IL-15 to the γc chain. 


Details of interactions between interleukin-15 (IL-15) and IL-15 Receptor α (IL-15Rα). Two salt-bridges by E53 and E46 of IL-15 and R26 and R35 of IL-15Rα, respectively, contribute substantiallyto the high affinity of the IL-15/IL-15Rα interaction.

Details of interactions between IL-34 and CSF-1 Receptor.



Molecular modeling and protein-protein docking

- provide structural models for proteins without available PDB structure
- model fusion proteins
- provide structural model of protein-protein complex interface

Cases studies

Models of IL-15, the sushi domain of IL-15Rα and the IL-15/IL-15Rα complex. The models (representation in ribbon or with the colored Connolly surface with a hydrophobicity index of (A) IL-15 and (B) IL-15Rα were obtained by homology modeling. (C) IL-15/IL-15Rα complex models were obtained using protein-protein docking programs.


Structural model of an IL-15-based fusion protein, named RLI


Development of a RLI-based immunocytokine (ICK) targeting the tumor-associated antigen GD2. (A) The C-terminus of the heavy chain of an anti-GD2 antibody was fused to the N-terminus of RLI. (B) The anti-GD2-RLI ICK not only efficiently bound to GD2 and IL-15 dimeric receptor IL-2Rb/gc , but also conserved both the cytotoxic effector functions of the antibody and the biological activity of the cytokine.


Structure-based virtual screening

to discover new hits for biological targets.

This activity is part of the regional project named PIRAMID and supported by la Région Pays de la Loire (, whose objective is the rational development of inhibitors of protein-protein interactions.

Cases studies

Discovery of small-molecule inhibitors impeding IL-15/IL-15R interaction. Pharmacophore and docking-based virtual screening of a large compound library led to the selection of one hit able to bind IL-15 and to inhibit in vitro functional effects. Its optimization by structure-activity relationship approach led to the discovery of the first small-molecule IL-15 inhibitor with sub-micromolar activity.


Selected Publications:
- Quéméner A., et al., (2019) J. Cell. Sci. 133(5):jcs236802.
- Quéménér A., et al., (2017) J. Med. Chem. 60:6249.
- Vincent M., et al., (2013) Int. J. Cancer 133:757.
- Vincent M., et al., (2013) Oncoimmunology 2:e26441.
- Bouchaud G., et al., (2008) J. Mol. Biol. 382:1.
- Mortier E., et al., (2006) J. Biol. Chem. 281:1612.
- Quéméner A., et al., (2006) Proteins 65:623.





Other Applications

Structural model 4-1BBLigand obtained by homology modeling. (A) Ribbon representation, with Connolly surface colored according to (B) a hydrophobicity index or (C) elelectrostatic potential.

Rabu C., et al., (2005) J. Biol. Chem. 280 :41472


Structures of Ras protein superfamily. (A) The Ras 3-dimensional structure is composed by 6-sheets and 5-helices. Conserved sequence motifs (G1-G5) involved in nucleotide binding are represented. (B) Similar resepresentation of Rho, Rab, Are, and Ran protein structure.

Loirand G., et al., (2013) Physiol. Rev. Biol. 93:1659.


Structural model of the protein CVP60 of European Brown Hare Syndrome Virus capsid obtained by homology modeling. P and S domains of the VP60 of the EBHSV capsid showing specific residues implicated in the epitopes of indicated mAbs.

Lopes A., et al., (2014) Virology. 468-470:104.

Identification of two novel variants in GP9 associated with Bernard-Soulier syndrome.

Boisseau P., et al., (2018) Platelets. 29:316.