A5082706216- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Scientific Computing and Data Management
- Bacteriophages and microbial interactions
- Data Visualization and Analytics
- Axon Guidance and Neuronal Signaling
- Bacterial Genetics and Biotechnology
- Nanopore and Nanochannel Transport Studies
- Bioinformatics and Genomic Networks
- Tuberculosis Research and Epidemiology
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Spectroscopy and Quantum Chemical Studies
- Machine Learning in Materials Science
- Hippo pathway signaling and YAP/TAZ
- Genetics, Bioinformatics, and Biomedical Research
- Neuroscience and Neuropharmacology Research
- Dark Matter and Cosmic Phenomena
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Receptor Mechanisms and Signaling
- Mycobacterium research and diagnosis
- Microfluidic and Capillary Electrophoresis Applications
Université de Toulouse
2018-2025
Centre National de la Recherche Scientifique
2013-2025
Laboratoire de Microbiologie et Génétique Moléculaires
2024-2025
Institut de Pharmacologie et de Biologie Structurale
2011-2024
Université Toulouse III - Paul Sabatier
2018-2024
University of Bristol
2024
Stockholm University
2023-2024
KTH Royal Institute of Technology
2023-2024
Science for Life Laboratory
2024
Laboratoire de Biochimie Théorique
2011-2023
The video games industry develops ever more advanced technologies to improve rendering, image quality, ergonomics and user experience of their creations providing very simple use tools design new games. In the molecular sciences, only a small number experts with specialized know-how are able interactive visualization applications, typically static computer programs that cannot easily be modified. Are there lessons learned from games? Could technology help us explore graphics ideas render...
Abstract Summary: The flexibility of α-helices is important for membrane protein function and calls better visualization analysis. Software presented that quantifies projects the helix axis evolution over time, with choice uniform or analytic heatmap graphics according to local geometry. Bendix supports static, molecular dynamics, atomistic coarse-grained input. Availability implementation: source code documentation, including installation instructions, are freely available at...
Teneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, FLRT proteins also expressed during murine cortical migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes reveal how lectin olfactomedin domains Latrophilin...
The ease with which a cell membrane can bend and deform is important for wide range of biological functions. Peripheral proteins that induce curvature in membranes (e.g. BAR domains) have been studied number years. Little known, however, about the effect integral on stiffness (characterised by bending rigidity, Kc). We demonstrate computer simulation adding at physiological densities alters membrane. First we establish coarse-grained MARTINI forcefield able to accurately reproduce rigidity...
Abstract Summary: The volume of an internal protein pocket is fundamental to ligand accessibility. Few programs that compute such volumes manage dynamic data from molecular dynamics (MD) simulations. Limited performance often prohibits analysis large datasets. We present Epock, efficient command-line tool calculates MD trajectories. A plugin for the VMD program provides a graphical user interface facilitate input creation, run Epock and analyse results. Availability implementation: C++...
The influenza virus is surrounded by an envelope composed of a lipid bilayer and integral membrane proteins. Understanding the structural dynamics provides biophysical insights into aspects viral function, such as wide-ranging survival times virion in different environments. We have combined experimental data from X-ray crystallography, nuclear magnetic resonance spectroscopy, cryo-electron microscopy, lipidomics to build model intact A virion. This basis microsecond-scale coarse-grained...
Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting adhesion repulsion, respectively. How the three function simultaneously is poorly understood. We show that Unc5D interacts FLRT2 in cis, controlling response to externally presented Lphn3. The ectodomains of bind cooperatively. Crystal structures ternary complex formed by extracellular domains reveal Lphn3 dimerizes when bound FLRT2:Unc5,...
Transduction of Hedgehog signals across the plasma membrane is facilitated by class F G-protein-coupled-receptor (GPCR) Smoothened (SMO). Recent studies suggest that SMO modulated via interactions its transmembrane (TM) domain with cholesterol. We apply molecular dynamics simulations embedded in cholesterol containing lipid bilayers, revealing a direct interaction TM at regions distinct from those observed A GPCRs. In particular extracellular tips helices TM2 and TM3 form well-defined site....
Cell membranes are crowded and complex environments. To investigate the effect of protein-lipid interactions on dynamic organization in mammalian cell membranes, we have performed coarse-grained molecular dynamics simulations containing >100 copies an inwardly rectifying potassium (Kir) channel which forms specific with regulatory lipid phosphatidylinositol 4,5-bisphosphate (PIP2). The tendency protein molecules to cluster has organizing membrane into compartments. At same time, diversity...
The exchange of ADP and ATP across the inner mitochondrial membrane is a fundamental cellular process. This facilitated by adenine nucleotide translocase, structure function which are critically dependent on signature phospholipid mitochondria, cardiolipin (CL). Here we employ multiscale molecular dynamics simulations to investigate CL interactions within environment. Using at both coarse-grained atomistic resolutions, identify three binding sites in agreement with those seen crystal...
Abstract The spatiotemporal organisation of membranes is often characterised by the formation large protein clusters. In Escherichia coli , outer membrane (OMP) clustering leads to OMP islands, which underpins turnover and drives across cell envelope. Modelling how islands form in order understand their origin behaviour has been confounded inherent difficulties simulating numbers OMPs over meaningful timescales. Here, we overcome these problems training a mesoscale model incorporating...
Phthiocerol dimycocerosate (DIM) is a major virulence factor of the pathogen Mycobacterium tuberculosis (Mtb). While this lipid promotes entry Mtb into macrophages, which occurs via phagocytosis, its molecular mechanism action unknown. Here, we combined biophysical, cell biology, and modeling approaches to reveal DIM on macrophage membranes leading first step infection. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry showed that molecules are...
Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures Uncoordinated-5 receptor D (Unc5D) in complex with morphogen glypican-3 (GPC3), forming an octameric glycoprotein complex. In complex, four Unc5D molecules pack into antiparallel bundle, flanked by GPC3 molecules. Central glycan-glycan are formed N-linked glycans emanating...
Abstract Ray casting on graphics processing units (GPUs) opens new possibilities for molecular visualization. We describe the implementation and calculation of diverse representations such as licorice, ball‐and‐stick, space‐filling van der Waals spheres, approximated solvent‐accessible surfaces using GPUs. introduce HyperBalls, an improved ball‐and‐stick representation replacing tubes, linking atom spheres by hyperboloids that can smoothly connect them. This type depiction is particularly...
Given the need for modern researchers to produce open, reproducible scientific output, lack of standards and best practices sharing data workflows used analyze molecular dynamics (MD) simulations has become an important issue in field. There are now multiple well-established packages perform simulations, often highly tuned exploiting specific classes hardware, each with strong communities surrounding them, but very limited interoperability/transferability options. Thus, choice software...
Mycobacterium tuberculosis ( Mtb ) is the causative agent of (TB), a disease that claims ~1.6 million lives annually. The current treatment regime long and expensive, missed doses contribute to drug resistance. Therefore, development new anti-TB drugs remains one highest public health priorities. has evolved complex cell envelope represents formidable barrier antibiotics. envelop consists four distinct layers enriched for specific lipids glycans. Although outer membrane, comprised mycolic...
The rise of open science and the absence a global dedicated data repository for molecular dynamics (MD) simulations has led to accumulation MD files in generalist repositories, constituting dark matter — that is technically accessible, but neither indexed, curated, or easily searchable. Leveraging an original search strategy, we found indexed about 250,000 2000 datasets from Zenodo, Figshare Open Science Framework. With focus on produced by Gromacs software, illustrate potential offered...
The functional importance of the methylation histidine 73 (H73) in actin remains unclear. Focusing on cytoplasmic β-actin, present all mammalian cells, we use molecular dynamics simulations with a polarizable force field and adaptive sampling to examine effects H73 methylation. Our results show that enhances nucleotide binding cleft opening, alters allosteric pathways connecting subdomains 2 4 (SD2 SD4) G-actin, affects backdoor openings inorganic phosphate release F-actin, as validated by...
We report the first assessment of blind predictions water positions at protein-protein interfaces, performed as part critical predicted interactions (CAPRI) community-wide experiment. Groups submitting docking for complex DNase domain colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict interfacial molecules using method their choice. The predictions-20 groups submitted a total 195 models-were assessed by measuring recall fraction water-mediated contacts. Of 176...