A5030610216- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Computational Drug Discovery Methods
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- Phytochemical compounds biological activities
- Identification and Quantification in Food
- Analytical Chemistry and Chromatography
- Advanced Biosensing Techniques and Applications
- Pharmacological Effects and Assays
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Cellular Mechanics and Interactions
- Vector-borne infectious diseases
- Bacterial Identification and Susceptibility Testing
- Bacterial Genetics and Biotechnology
- Yersinia bacterium, plague, ectoparasites research
- Monoclonal and Polyclonal Antibodies Research
Institut Pasteur
2020-2023
Université Paris Cité
2015-2023
Centre National de la Recherche Scientifique
2013-2023
Centre de Biologie Structurale
2021
École Polytechnique
2013-2020
Sorbonne Paris Cité
2015-2018
Sorbonne Université
2018
Laboratoire de Biochimie Théorique
2018
Université Paris Sciences et Lettres
2018
Institut de Biologie Physico-Chimique
2018
Generating top-down tandem mass spectra (MS/MS) from complex mixtures of proteoforms benefits improvements in fractionation, separation, fragmentation, and analysis. The algorithms to match MS/MS sequences have undergone a parallel evolution, with both spectral alignment match-counting approaches producing high-quality proteoform-spectrum matches (PrSMs). This study assesses state-of-the-art for identification (ProSight PD, TopPIC, MSPathFinderT, pTop) their yield PrSMs while controlling...
Genetic feedback control represents a central paradigm in regulation of biological systems and their response to environmental change. Vector-borne pathogens have evolved complex developmental programs adapt very distinct host environments, but the relevance stage differentiation remains be elucidated. Here we address this open question trypanosomatid parasite Leishmania that shows constitutive gene transcription, thus providing unique model system assess post-transcriptional mechanisms...
We describe an automated procedure for protein design, implemented in a flexible software package, called Proteus. System setup and calculation of energy matrix are done with the XPLOR modeling program its sophisticated command language, supporting several force fields solvent models. A second provides algorithms to search sequence space. It allows decomposition system into groups, which can be combined different ways function, both positive negative design. The whole controlled by editing...
One avenue to address the paucity of clinically testable targets is reinvestigate druggable genome by tackling complicated types such as Protein-Protein Interactions (PPIs). Given challenge target those interfaces with small chemical compounds, it has become clear that learning from successful examples PPI modulation a powerful strategy. Freely accessible databases modulators provide community tractable and pharmacological data, well tools query them, are therefore essential stimulate new...
Proteomic and transcriptomic technologies resulted in massive biological datasets, their interpretation requiring sophisticated computational strategies. Efficient intuitive real-time analysis remains challenging. We use proteomic data on 1417 proteins of the green microalga Chlamydomonas reinhardtii to investigate physicochemical parameters governing selectivity three cysteine-based redox post translational modifications (PTM): glutathionylation (SSG), nitrosylation (SNO) disulphide bonds...
Abstract In antibody‐based drug research, a complete characterization of antibody proteoforms covering both the amino acid sequence and all posttranslational modifications remains major concern. The usual mass spectrometry‐based approach to achieve this goal is bottom‐up proteomics, which relies on digestion antibodies but does not allow diversity be assessed. Middle‐down top‐down approaches have recently emerged as attractive alternatives are yet mastered thus used in routine by many...
Molecular dynamics simulations and normal mode analysis are well-established approaches to generate receptor conformational ensembles (RCEs) for ligand docking virtual screening. Here, we report new fast molecular dynamics-based analysis-based protocols combined with pocket classifications efficiently RCEs.We assessed our on two well-characterized protein targets showing local active site flexibility, dihydrofolate reductase large collective movements, CDK2. The performance of the RCEs was...
D-Amino acids are largely excluded from protein synthesis, yet they of great interest in biotechnology. Unnatural amino have been introduced into proteins using engineered aminoacyl-tRNA synthetases (aaRSs), and this strategy might be applicable to D-amino acids. Several aaRSs can aminoacylate their tRNA with a acid; these, tyrosyl-tRNA synthetase (TyrRS) has the weakest stereospecificity. We use computational design suggest active site mutations Escherichia coli TyrRS that could increase...
Protein-protein interactions (PPIs) are key elements in numerous biological pathways and the subject of a growing number drug discovery projects including against infectious diseases. Designing drugs on PPI targets remains difficult task requires extensive efforts to qualify given interaction as an eligible target. To this end, besides evident need determine role PPIs disease-associated their experimental characterization therapeutics targets, prediction capacity be bound by other protein...
We describe methods for physics-based protein design and some recent applications from our work. present the physical interpretation of a MC simulation in sequence space show that sequences conformations form well-defined statistical ensemble, explored with Monte Carlo Boltzmann sampling. The folded state energy combines molecular mechanics solutes continuum electrostatics solvent. usually assume one or few fixed backbone structures discrete side chain rotamers. Methods based on dynamics,...
A computational protein design method is extended to allow Monte Carlo simulations where two ligands are titrated into a binding pocket, yielding free energy differences. These provide stringent test of the physical model, including surface and sidechain rotamer definition. As test, we consider tyrosyl-tRNA synthetase (TyrRS), which has been extensively redesigned experimentally. We its specificity for substrate l-tyrosine (l-Tyr), compared analogs d-Tyr, p-acetyl-, p-azido-phenylalanine...
Multistate protein design explores side chain mutations, with the backbone allowed to sample a small, predetermined library of conformations. To achieve Boltzmann sampling sequences and conformations, we use hybrid Monte Carlo (MC) scheme: trial hop between models is followed by short MC segment where rotamers adjust new backbone, before applying Metropolis-like acceptance test. The theoretical form practical approximation for test are derived. We then compute conformational free energies...
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Abstract Background Harmonin Homogy Domains (HHD) are recently identified orphan domains of about 70 residues folded in a compact five alpha-helix bundle that proved to be versatile terms function, allowing for direct binding partner as well regulating the affinity and specificity adjacent their own targets. Adding small size rather simple fold, HHDs appear convenient modules regulate protein–protein interactions various biological contexts. Surprisingly, only nine have been detected six...
Abstract MSclassifR is an R package that has been specifically designed to improve the classification of mass spectra obtained from MALDI-TOF spectrometry. It offers a comprehensive range functions are focused on processing spectra, identifying discriminant m/z values, and making accurate predictions. The introduces innovative algorithms for selecting discriminating values To assess effectiveness these methods, extensive tests were conducted using challenging real datasets, including...
A bstract Motivation Protein-protein interactions (PPIs) are key elements in numerous biological pathways and the subject of a growing number drug discovery projects including against infectious diseases. Designing drugs on PPI targets remains difficult task requires extensive efforts to qualify given interaction as an eligible target. To this end, besides evident need determine role PPIs disease-associated their experimental characterization therapeutics targets, prediction capacity be...
Abstract We describe methods and software for physics-based protein design. The folded state energy combines molecular mechanics with Generalized Born solvent. Sequence conformation space are sampled Replica Exchange Monte Carlo, assuming one or a few fixed backbone structures discrete side chain rotamers. Whole design enzyme presented as illustrations. Full redesign of three PDZ domains was done using simple, empirical, unfolded model. Designed sequences were very similar to natural ones....
ABSTRACT In antibody-based drug research, regulatory agencies request a complete characterization of antibody proteoforms covering both the amino acid sequence and all post-translational modifications. The usual mass spectrometry-based approach to achieve this goal is bottom-up proteomics, which relies on digestion antibodies, but does not allow diversity be assessed. Middle-down top-down approaches have recently emerged as attractive alternatives are yet mastered thus used in routine by...