CV Science

Bruno Villoutreix Structural bioinformatics and AI-powered drug design

Course and current status

Bruno Villoutreix is Research Director at Inserm (DR1), the French National Institute of Health and Medical Research. For more than ten years, he headed the Inserm research unit Therapeutic Molecules in Silico (MTi).

For more than 25 years, he has worked at the interface of molecular medicine, structural bioinformatics, chemoinformatics and computer-aided drug discovery, in both academic and private-sector environments in several countries. His biomedical research has mainly focused on cancer, the complement system and blood coagulation.

His work combines AI/machine-learning approaches, molecular modelling and other computational methods with experimental studies carried out in close collaboration with biologists and clinicians. He develops computational tools and workflows, and also adapts and integrates existing methods using his expertise in structural biology, chemistry and drug discovery.
These approaches are used to identify and optimize drug candidates and chemical probes, including small molecules and peptides, to investigate challenging therapeutic targets and to better understand disease-associated molecular mechanisms. He has contributed to the development of several chemical probes, including a molecule initially identified through in silico approaches that is currently undergoing clinical evaluation. His work has also addressed therapeutic protein stabilization, monoclonal antibody optimization and drug repurposing.
Together with collaborators, he has developed software packages, databases and online drug-discovery services used by the scientific community. He also develops educational resources, short courses and videos on AI-powered drug design and on emerging AI technologies for scientific research, including agentic coding and local AI tools (https://www.youtube.com/@AI-Biotech-Studio).

Since September 2020, he has been affiliated with Inserm UMR 1141 at Robert-Debré Hospital, Paris.

Scientific summary

More than 240 publications | Google Scholar H-index: 67 | approximately 15,300 citations | 15 patents

Bruno Villoutreix's current research focuses on AI-powered and structure-based drug discovery, particularly for challenging therapeutic targets such as protein-protein interactions.

His research strategy integrates several complementary approaches:
    •    development and application of AI/machine-learning methods for drug discovery and ADME-Tox prediction;
    •    structure-based molecular modelling, virtual screening and rational design of small molecules, peptides and proteins;
    •    AI-generated molecules;
    •    development, adaptation and integration of computational tools for specific biomedical questions;
    •    analysis of disease-associated genetic variants and their effects on protein structure and function;
    •    close integration of computational predictions with experimental validation through collaborations with biologists and clinicians.

He has contributed with collaborators to the development of several freely accessible computational resources, including:
    •    FAF-Drugs, an online platform for simple ADME-Tox filtering and compound property assessment;
    •    FastTargetPred, a computational tool for ligand-based target profiling;
    •    MTiOpenScreen, an online platform for structure-based virtual screening…

He also maintains VLS3D (https://www.vls3d.com/), which provides access to and guidance on numerous computational resources relevant to virtual screening, molecular modelling and drug discovery.
A further component of his activity is scientific training and dissemination. He develops short courses, tutorials and videos on AI-powered drug design and on the practical use of emerging AI technologies in research, including generative AI, agentic coding and local AI systems (https://www.youtube.com/@AI-Biotech-Studio).

Some selected publications/reviews:

1. Virard F, Giraud S, Bonnet M, Magadoux L, Martin L, Pham TH, Skafi N, Deneuve S, Frem R, Villoutreix BO, Sleiman NH, Reboulet J, Merabet S, Chaptal V, Chaveroux C, Hussein N, Aznar N, Fenouil T, Treilleux I, Saintigny P, Ansieau S, Manié S, Lebecque S, Renno T, Coste I. Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death. Nat Commun. 2024
2. Pernot S, Tomé M, Galeano-Otero I, Evrard S, Badiola I, Delom F, Fessart D, Smani T, Siegfried G, Villoutreix BO, Khatib AM. Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium activity repression. Front Immunol. 2024
3. Singh N, Chaput L, Villoutreix BO. Fast Rescoring Protocols to Improve the Performance of Structure-Based Virtual Screening Performed on Protein-Protein Interfaces. J Chem Inf Model. 2020 Aug 24;60(8):3910-3934.
4. Singh N, Chaput L, Villoutreix BO. Virtual screening web servers: designing chemical probes and drug candidates in the cyberspace. Brief Bioinform. 2021 Mar 22;22(2):1790-1818.
5. Villoutreix BO, Calvez V, Marcelin AG, Khatib A-M. In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2-Spike RBD Interface. Int J Mol Sci. 2021 Feb 8;22(4):1695.
6. Habault J, Thonnart N, Pasquereau-Kotula E, Bagot M, Bensussan A, Villoutreix BO, Marie-Cardine A, Poyet JL. PAK1-Dependent Antitumor Effect of AAC-11‒Derived Peptides on Sézary Syndrome Malignant CD4+ T Lymphocytes. J Invest Dermatol. 2021
7. Gyulkhandanyan A, Rezaie AR, Roumenina L, Lagarde N, Fremeaux-Bacchi V, Miteva MA, Villoutreix BO. Analysis of protein missense alterations by combining sequence- and structure-based methods. Mol Genet Genomic Med. 2020 Apr;8(4):e1166.
8. Villoutreix BO, Beaune PH, Tamouza R, Krishnamoorthy R, Leboyer M. Prevention of COVID-19 by drug repurposing: rationale from drugs prescribed for mental disorders. Drug Discov Today. 2020 Aug;25(8):1287-1290.
9. Soulet F, Bodineau C, Hooks KB, Descarpentrie J, Alves I, Dubreuil M, Mouchard A, Eugenie M, Hoepffner JL, López JJ, Rosado JA, Soubeyran I, Tomé M, Durán RV, Nikolski M, Villoutreix BO, Evrard S, Siegfried G, Khatib AM. ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation. JCI Insight. 2020 Jul 23;5(14):e129070.
10. Nougarede A, Popgeorgiev N, Kassem L, Omarjee S, Borel S, Mikaelian I, Lopez J, Gadet R, Marcillat O, Treilleux I, Villoutreix BO, Rimokh R, Gillet G. Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10. Cancer Res. 2018 Mar 15;78(6):1404-1417.
11. Louet M, Bitam S, Bakouh N, Bignon Y, Planelles G, Lagorce D, Miteva MA, Eladari D, Teulon J, Villoutreix BO. In silico model of the human ClC-Kb chloride channel: pore mapping, biostructural pathology and drug screening. Sci Rep. 2017 Aug 3;7(1):7249.
12. Lagorce D, Bouslama L, Becot J, Miteva MA, Villoutreix BO. FAF-Drugs4: free ADME-tox filtering computations for chemical biology and early stages drug discovery. Bioinformatics. 2017 Nov 15;33(22):3658-3660.
13. Labbé CM, Kuenemann MA, Zarzycka B, Vriend G, Nicolaes GA, Lagorce D, Miteva MA, Villoutreix BO, Sperandio O. iPPI-DB: an online database of modulators of protein-protein interactions. Nucleic Acids Res. 2016 Jan 4;44(D1):D542-7.
14. Nicolaes GA, Kulharia M, Voorberg J, Kaijen PH, Wroblewska A, Wielders S, Schrijver R, Sperandio O, Villoutreix BO. Rational design of small molecules targeting the C2 domain of coagulation factor VIII. Blood. 2014 Jan 2;123(1):113-20
15. Segers K, Sperandio O, Sack M, Fischer R, Miteva MA, Rosing J, Nicolaes GA, Villoutreix BO. Design of protein membrane interaction inhibitors by virtual ligand screening, proof of concept with the C2 domain of factor V. Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12697-702.