1982: CNRS Researcher, Theoretical Biochemistry Laboratory, IBPC, Paris.
1999-Present: Professor University Paris-Diderot, Biochemistry and Life Sciences Department.
1999-2005: Member of UMR-S726, “Genomics Bioinformatics and Molecular Modelling” (EBGM). Molecular Modelling group leader
2005-2008: Director of UMR-S726.
2009-2018: Team Leader of DSIMB, “Dynamic of Structures and Interactions of Macromolecules in Biology” UMR_S1134” Integrated Red Blood Cell Physiology. University Paris Diderot-Inserm and Institut National de la Transfusion Sanguine (INTS)
2019-Present: Leader of Molecular Modelling Group in DSIMB.
Responsibilities at the University and National Institutions.
2004-2008: Vice-President of the French Biophysical Society.
2014-2019: Vice President of French National Board of Universities (CNU) Section “Biochemistry and Molecular Biology”. This national board qualifies biochemists and molecular biologists for lecturer or professor positions, which is required before applying for positions in University.
2009- : Administration Council of Life Sciences Department in Paris-Diderot University (Elected member)
2018-2019: Research Commission of the Paris-Diderot University (Elected member).
2018-2019: President of Scientific Strategy and Evaluation commission of Paris-Diderot University
2019-2023: Administrative Board of Faculty of Sciences of “Université de Paris” (Elected member)
EDUCATION
1979 Maîtrise Physical-Chemistry (Eq. Bachelor Degree) Pierre et Marie Curie-Paris VI University
1980 DEA Physical-Chemistry (Eq. Master Degree) Pierre et Marie Curie-Paris VI University
1983 3rd Cycle Doctorate Physical-Chemistry (Eq. PhD) Pierre et Marie Curie-Paris VI University
1987 State Doctorate (Eq. Habilitation) Pierre et Marie Curie-Paris VI University
RESEARCH INTERESTS
Membrane Protein Systems, Molecular Mechanisms, Biophysics, Molecular Modelling, Structural Bioinformatics.
Investigating the Dynamics of the KCNN4 Channel: From the Determination of the Complete K+ Permeation Pathway Across the Channel to Its Opening by PIP2 Stephane Jedele, Benoit Allegrini, Hélène Guizouarn, Catherine Etchebest Journal of Chemical Information and Modeling, 2025 KCNN4 is a calcium (Ca)-activated potassium channel for which Ca2+ sensitivity is conferred by calmodulin (CaM) that constitutively binds to the channel. Until the main part of the structure bound to CaM has been resolved, in silico studies had used homology models derived from the well characterized transmembrane domain of other K+ channels, limiting the functional investigation to this particular region. Thus, how the regulatory domains of KCNN4 communicate with each other and where the possible gates are located across the complete structure are still not well understood. Here we present for the first time results obtained from the investigation of full-length models of the channel in different conformational states and molecular contexts using classical all-atom molecular dynamic simulations. The simulations covered two activated states (open and closed) and a preactivated state of the channel embedded in a simple membrane model and a model of red blood cell membrane, where the channel is functionally expressed in vivo. Surprisingly, the intracellular domain was refractory to the entrance of K+, whatever the state of the channel was, allowing the K+ ions to enter and exit the channel only through two newly identified restrained diffusion spots. Inside the channel, the K+ flux was controlled by the V282 residue closing the pore region when the CaM N-lobes were not bound. This flux was compatible with the passage of fully or partially hydrated K+, depending on the opening level. Finally, the presence of phosphatidylinositol-4,5-bisphosphate (PIP2), a well-known K+-channel modulator, in a putative binding site of KCNN4 clearly facilitated the opening of the V282 restriction. Thus, in addition to the elucidation of the possible complete K+ permeation pathway throughout KCNN4, our results confirmed the direct activatory role of PIP2, associated with the channel opening, and provide a first insight into the architecture and the behavior of the complete intracellular region of KCNN4.
Evaluation of Transmembrane Protein Structural Models Using HPMScore Stéphane Téletchéa, Jérémy Esque, Aurélie Urbain, Catherine Etchebest, Alexandre G. de Brevern Biomedinformatics, 2023 Transmembrane proteins (TMPs) are a class of essential proteins for biological and therapeutic purposes. Despite an increasing number of structures, the gap with the number of available sequences remains impressive. The choice of a dedicated function to select the most probable/relevant model among hundreds is a specific problem of TMPs. Indeed, the majority of approaches are mostly focused on globular proteins. We developed an alternative methodology to evaluate the quality of TMP structural models. HPMScore took into account sequence and local structural information using the unsupervised learning approach called hybrid protein model. The methodology was extensively evaluated on very different TMP all-α proteins. Structural models with different qualities were generated, from good to bad quality. HPMScore performed better than DOPE in recognizing good comparative models over more degenerated models, with a Top 1 of 46.9% against DOPE 40.1%, both giving the same result in 13.0%. When the alignments used are higher than 35%, HPM is the best for 52%, against 36% for DOPE (12% for both). These encouraging results need further improvement particularly when the sequence identity falls below 35%. An area of enhancement would be to train on a larger training set. A dedicated web server has been implemented and provided to the scientific community. It can be used with structural models generated from comparative modeling to deep learning approaches.
General Trends of the Camelidae Antibody VHHs Domain Dynamics Akhila Melarkode Vattekatte, Julien Diharce, Joseph Rebehmed, Frédéric Cadet, Fabrice Gardebien, et al. International Journal of Molecular Sciences, 2023 Conformational flexibility plays an essential role in antibodies’ functional and structural stability. They facilitate and determine the strength of antigen–antibody interactions. Camelidae express an interesting subtype of single-chain antibody, named Heavy Chain only Antibody. They have only one N-terminal Variable domain (VHH) per chain, composed of Frameworks (FRs) and Complementarity Determining regions (CDRs) like their VH and VL counterparts in IgG. Even when expressed independently, VHH domains display excellent solubility and (thermo)stability, which helps them to retain their impressive interaction capabilities. Sequence and structural features of VHH domains contributing to these abilities have already been studied compared to classical antibodies. To have the broadest view and understand the changes in dynamics of these macromolecules, large-scale molecular dynamics simulations for a large number of non-redundant VHH structures have been performed for the first time. This analysis reveals the most prevalent movements in these domains. It reveals the four main classes of VHHs dynamics. Diverse local changes were observed in CDRs with various intensities. Similarly, different types of constraints were observed in CDRs, while FRs close to CDRs were sometimes primarily impacted. This study sheds light on the changes in flexibility in different regions of VHH that may impact their in silico design.
Quality assessment of VHH models Aravindan Arun Nadaradjane, Julien Diharce, Joseph Rebehmed, Frédéric Cadet, Fabrice Gardebien, et al. Journal of Biomolecular Structure and Dynamics, 2023
Discrete analyses of protein dynamics Tarun Jairaj Narwani, Pierrick Craveur, Nicolas K. Shinada, Aline Floch, Hubert Santuz, et al. Journal of Biomolecular Structure and Dynamics, 2020
Conformational dynamics study of TfR1 upon transferrin binding via NMA and MD simulations M Zemmouche, G Falque, F Cadet, F Gardebien, C Etchebest Journal of Molecular Graphics and Modelling, 109379 , 2026 2026
ARID-sf: A physics-informed Deep Learning scoring function to improve Antibody-Antigen docking model ranking I Grandguillaume, C Etchebest, FLB da Silva bioRxiv, 2026.01. 20.700530 , 2026 2026
Impact of the N-glycosylation on full-length IgG2 and IgG4 antibodies: a comparative study using molecular dynamics simulations. R Leon Foun Lin, A Bellaiche, J Diharce, C Etchebest bioRxiv, 2026.04. 14.718417 , 2026 2026
ANABAG: Annotated Antibody–Antigen Data Set with Unique Features for Antibody Engineering Applications I Grandguillaume, FL Barroso da Silva, C Etchebest Journal of Chemical Information and Modeling 65 (20), 11454-11472 , 2025 2025 Citations: 2
The key role of the dynamics and flexibility of proteins in functional mechanisms: How computational methods can contribute to their identification. RLF Lin, A Bellaiche, C Etchebest Biochimie , 2025 2025 Citations: 3
Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis C Berenguier, X Chen, B Allegrini, H Guizouarn, F Borgese, C Etchebest, ... Oncogene 44 (31), 2715-2729 , 2025 2025 Citations: 3
Multiscale in silico modeling and simulation of an antibody at ultra-low temperatures: impact of cryoprotectants and insights into the dimerization phenomenon LFL Ravy, J Diharce, C Etchebest FEBS OPEN BIO 15, 46-46 , 2025 2025
Investigating the Dynamics of the KCNN4 Channel: From the Determination of the Complete K + Permeation Pathway Across the Channel to Its Opening by PIP2 S Jedele, B Allegrini, H Guizouarn, C Etchebest Journal of Chemical Information and Modeling 65 (4), 2116-2128 , 2025 2025 Citations: 3
Computational study of the antibody-antigen properties to develop binders for viral proteins IPAJ Grandguillaume, FLB Silva, CJC Etchebest 2025
Transposable element exonization generates a reservoir of evolving and functional protein isoforms YA Arribas, B Baudon, M Rotival, G Suárez, PE Bonté, V Casas, ... Cell 187 (26), 7603-7620. e22 , 2024 2024 Citations: 45
The mutual and dynamic role of TSPO and ligands in their binding process: an example with PK-11195 RM Rao, I El Dhaybi, F Cadet, C Etchebest, J Diharce Biochimie 224, 29-40 , 2024 2024 Citations: 3
The Barroso Research lab: biomolecular interactions, computing, and data-driven science to understand and engineer biological and pharmaceutical systems in a global academic … FLB da Silva, C Etchebest, EE Santiso, CC Giron, I Grandguillaume, ... Journal of Information and Data Management 15 (1), 242-254 , 2024 2024
Quality assessment of V H H models AA Nadaradjane, J Diharce, J Rebehmed, F Cadet, F Gardebien, JC Gelly, ... Journal of Biomolecular Structure and Dynamics 41 (22), 13287-13301 , 2023 2023 Citations: 7
Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with … B Allegrini, LD Nguyen, M Mignotet, C Etchebest, O Fenneteau, J Platon, ... Blood Cells, Molecules, and Diseases 103, 102780 , 2023 2023
Evaluation of transmembrane protein structural models using HPMScore S Téletchéa, J Esque, A Urbain, C Etchebest, AG de Brevern BioMedInformatics 3 (2), 306-326 , 2023 2023 Citations: 8
Molecular and structural characterization of a novel high‐prevalence antigen of the Augustine blood group system C Vrignaud, M Mikdar, R Duval, L Reininger, VL Damaraju, M Sawyer, ... Transfusion 63 (3), 610-618 , 2023 2023 Citations: 1
General Trends of the Camelidae Antibody V H Hs Domain Dynamics AM Vattekatte, J Diharce, J Rebehmed, F Cadet, F Gardebien, ... International journal of molecular sciences 24 (5), 4511 , 2023 2023 Citations: 6
Analysis of VHH dynamics AM Vattekatte, J Diharce, C Etchebest, A de Brevern 67th Biophysical Society Annual Meeting , 2023 2023
NS1 from two Zika virus strains differently interact with a membrane: Insights to understand their differential virulence SA Poveda Cuevas, FL Barroso da Silva, C Etchebest Journal of Chemical Information and Modeling 63 (4), 1386-1400 , 2023 2023 Citations: 11
Data Mining and Machine Learning over HPC Approach Enhancing Antibody Conformations Prediction DRG Zanfack, A Bellaïche, C Etchebest, S Dhiman, V Gadhamshetty, ... Microbial Stress Response: Mechanisms and Data Science, 75-92 , 2023 2023 Citations: 2
MOST CITED SCHOLAR PUBLICATIONS
A new approach to the rapid determination of protein side chain conformations P Tuffery, C Etchebest, S Hazout, R Lavery Journal of Biomolecular structure and dynamics 8 (6), 1267-1289 , 1991 1991 Citations: 453
Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks AG de Brevern, C Etchebest, S Hazout Proteins: Structure, Function, and Bioinformatics 41 (3), 271-287 , 2000 2000 Citations: 418
Determining membrane protein structures: still a challenge! JJ Lacapere, E Pebay-Peyroula, JM Neumann, C Etchebest Trends in biochemical sciences 32 (6), 259-270 , 2007 2007 Citations: 257
Amphipathic lipid packing sensor motifs: probing bilayer defects with hydrophobic residues S Vanni, L Vamparys, R Gautier, G Drin, C Etchebest, PFJ Fuchs, ... Biophysical journal 104 (3), 575-584 , 2013 2013 Citations: 247
A Model for the Photosystem II Reaction Center Core Including the Structure of the Primary Donor P 680 , B Svensson, C Etchebest, P Tuffery, P Van Kan, J Smith, S Styring Biochemistry 35 (46), 14486-14502 , 1996 1996 Citations: 246
Conical lipids in flat bilayers induce packing defects similar to that induced by positive curvature L Vamparys, R Gautier, S Vanni, WFD Bennett, DP Tieleman, B Antonny, ... Biophysical journal 104 (3), 585-593 , 2013 2013 Citations: 233
Predicting protein flexibility through the prediction of local structures A Bornot, C Etchebest, AG De Brevern Proteins: Structure, Function, and Bioinformatics 79 (3), 839-852 , 2011 2011 Citations: 211
Comparison of three algorithms for the assignment of secondary structure in proteins: the advantages of a consensus assignment N Colloc'h, C Etchebest, E Thoreau, B Henrissat, JP Mornon Protein Engineering, Design and Selection 6 (4), 377-382 , 1993 1993 Citations: 190
Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis H Sklenar, C Etchebest, R Lavery Proteins: Structure, Function, and Bioinformatics 6 (1), 46-60 , 1989 1989 Citations: 183
A structural alphabet for local protein structures: improved prediction methods C Etchebest, C Benros, S Hazout, AG de Brevern Proteins: Structure, Function, and Bioinformatics 59 (4), 810-827 , 2005 2005 Citations: 165
Unraveling proteins: a molecular mechanics study R Rohs, C Etchebest, R Lavery Biophysical journal 76 (5), 2760-2768 , 1999 1999 Citations: 145
A short survey on protein blocks AP Joseph, G Agarwal, S Mahajan, JC Gelly, LS Swapna, B Offmann, ... Biophysical reviews 2 (3), 137-145 , 2010 2010 Citations: 139
On the orientation of a designed transmembrane peptide: toward the right tilt angle? S Özdirekcan, C Etchebest, JA Killian, PFJ Fuchs Journal of the American Chemical Society 129 (49), 15174-15181 , 2007 2007 Citations: 129
Dynamical properties of the MscL of Escherichia coli: a normal mode analysis H Valadie, JJ Lacapčre, YH Sanejouand, C Etchebest Journal of molecular biology 332 (3), 657-674 , 2003 2003 Citations: 128
Protein flexibility in the light of structural alphabets P Craveur, AP Joseph, J Esque, TJ Narwani, F Noel, N Shinada, ... Frontiers in molecular biosciences 2, 20 , 2015 2015 Citations: 123
PredyFlexy: flexibility and local structure prediction from sequence AG de Brevern, A Bornot, P Craveur, C Etchebest, JC Gelly Nucleic acids research 40 (W1), W317-W322 , 2012 2012 Citations: 122
Antioxidant and membrane binding properties of serotonin protect lipids from oxidation S Azouzi, H Santuz, S Morandat, C Pereira, F Côté, O Hermine, K El Kirat, ... Biophysical journal 112 (9), 1863-1873 , 2017 2017 Citations: 113
A reduced amino acid alphabet for understanding and designing protein adaptation to mutation C Etchebest, C Benros, A Bornot, AC Camproux, AG De Brevern European Biophysics Journal 36 (8), 1059-1069 , 2007 2007 Citations: 113
New insights into GluT1 mechanics during glucose transfer T Galochkina, M Ng Fuk Chong, L Challali, S Abbar, C Etchebest Scientific reports 9 (1), 998 , 2019 2019 Citations: 107
A structural model of a seven-transmembrane helix receptor: the Duffy antigen/receptor for chemokine (DARC) AG De Brevern, H Wong, C Tournamille, Y Colin, C Le van Kim, ... Biochimica et Biophysica Acta (BBA)-General Subjects 1724 (3), 288-306 , 2005 2005 Citations: 104
