Computational Modeling of Protein-Ligand Interactions

Head: Pierre Tufféry (DR INSERM)

INSERM team U1133


The team’s work, prior to 2019, was carried out within the UMRS Paris Diderot-Inserm 973 (MTi)


Computational approaches are now well established components of the pipelines for rational drug candidates. However, they have to continuously adapt to face the emerging challenges in the field. Firstly, the one drug – one target paradigm is shifting towards a more holistic and realistic vision of the drug effect on a system. The integration of large and diverse sources of data from chemistry and biology coupled with the development and the application of new computational approaches give the opportunity to provide a more complete pharmacological profile of a drug. For instance, knowing the ensemble of the targets on which a molecule can interact with, in a specific or non-specific manner is important in the design of promiscuous drugs, drug repurposing, and the understanding of adverse effects associated to a drug. Secondly, new classes of molecules such as peptides or antibodies are emerging as interesting alternatives to small molecules. They  address the limits reached by small compounds by exploring new chemical spaces for new categories of targets (allostery, protein-protein interface, …).

Our team focuses on these issues by the development of new methods, protocols, and their application on 2 complementary directions:

(i) Pharmacological profiling (leaders: AC. Camproux and O. Taboureau) that includes structural protein and binding site exploration, prediction of ligand-protein profiles and interactions (including biostatistical approaches), and ligand-phenotypes relationship (with the integration of systems biology).

(ii) Peptide design (leader : P. Tuffery), with a special focus on interfering peptides, i.e. peptides able to interfere speficically with target protein-protein interactions. Among our skills : the identification and structural characterization of peptides, peptide-protein interactions – identification of binding sites, interaction energy – and candidate peptide optimization.


The team also hosts the RPBS platform (Ressource Parisienne en Bioinformatique Structurale (, a member of the French Institute for Bioinformatics (IFB) and the ChemBioFrance infrastructure.


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