Publications de Stéphane Rosset

Exploring “dark-matter” protein folds using deep learning

Pierre Vandergheynst, Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Andreas Loukas, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais, Casper Alexander Goverde

De novo protein design explores uncharted sequence and structure space to generate novel proteins not sampled by evolution. A main challenge in de novo design involves crafting “designable” structural templates to guide the sequence searches toward adoptin ...

2024

A deep mutational scanning platform to characterize the fitness landscape of anti-CRISPR proteins

Bruno Emanuel Ferreira De Sousa Correia, Stéphane Rosset

Deep mutational scanning is a powerful method for exploring the mutational fitness landscape of proteins. Its adaptation to anti-CRISPR proteins, which are natural CRISPR-Cas inhibitors and key players in the co-evolution of microbes and phages, facilitate ...

2024

Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies

Bruno Emanuel Ferreira De Sousa Correia, Sabrina Susan Vollers, Andreas Scheck, Stéphane Rosset

Hepatitis C virus (HCV) infection causes similar to 290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among the ...

AMER ASSOC ADVANCEMENT SCIENCE2024

Computational design of soluble and functional membrane protein analogues

Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Stéphane Rosset, Casper Alexander Goverde, Martin Pacesa

De novo design of complex protein folds using solely computational means remains a substantial challenge1. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, ...

2024

Rational Design of Chemically Controlled Antibodies and Protein Therapeutics

Sandrine Madeleine Suzanne Georgeon, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Pablo Gainza Cirauqui, Li Tang, Sailan Shui, Stéphane Rosset, Lucia Bonati, Leo Scheller

Protein-based therapeutics, such as monoclonal antibodies and cytokines, are important therapies for various pathophysiological conditions such as oncology, autoimmune disorders, and viral infections. However, the wide application of such protein therapeut ...

2023

De novo design of protein interactions with learned surface fingerprints

Henning Paul-Julius Stahlberg, Didier Trono, Priscilla Turelli, Charlène Mireille Raymonde Raclot, Sandrine Madeleine Suzanne Georgeon, Beat Fierz, Aaron Simone Petruzzella, Anthony Marchand, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Zander Harteveld, Pablo Gainza Cirauqui, Freyr Sverrisson, Andreas Scheck, Sarah Wehrle, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais, Alexandra Teslenko, Jane Marsden, Michael Bronstein, Casper Alexander Goverde, Stephen Michael Buckley, Dongchun Ni, Martin Pacesa

Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This k ...

2023

De novo protein design by inversion of the AlphaFold structure prediction network

Bruno Emanuel Ferreira De Sousa Correia, Stéphane Rosset, Casper Alexander Goverde, Benedict Dieter Gregor Wolf, Hamed Khakzad

De novo protein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology through the engineering of novel protein functionalities. Despite recent progress in comp ...

2023

A generic framework for hierarchical de novo protein design

Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Stéphane Rosset

De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test for our understanding of the underlying physical principles of protein folding and may ...

National Academy of Sciences2022

Assessing and enhancing foldability in designed proteins

Bruno Emanuel Ferreira De Sousa Correia, Che Yang, Stéphane Rosset

Recent advances in protein-design methodology have led to a dramatic increase in reliability and scale. With these advances, dozens and even thousands of designed proteins are automatically generated and screened. Nevertheless, the success rate, particular ...

WILEY2022

RosettaSurf-A surface-centric computational design approach

Pierre Vandergheynst, Michaël Defferrard, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Andreas Loukas, Andreas Scheck, Stéphane Rosset

Proteins are typically represented by discrete atomic coordinates providing an accessible framework to describe different conformations. However, in some fields proteins are more accurately represented as near-continuous surfaces, as these are imprinted wi ...

PUBLIC LIBRARY SCIENCE2022

De Novo Design of Site-specific Protein Binders Using Surface Fingerprints

Sandrine Madeleine Suzanne Georgeon, Aaron Simone Petruzzella, Elisa Oricchio, Zander Harteveld, Pablo Gainza Cirauqui, Freyr Sverrisson, Andreas Scheck, Sarah Wehrle, Stéphane Rosset, Alexandra Krina Van Hall-Beauvais

WILEY2021

A Rosetta-based protein design protocol converging to natural sequences

Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Giulia Sormani, Stéphane Rosset

Computational protein design has emerged as a powerful tool capable of identifying sequences compatible with pre-defined protein structures. The sequence design protocols, implemented in the Rosetta suite, have become widely used in the protein engineering ...

AMER INST PHYSICS2021

Bottom-up de novo design of functional proteins with complex structural features

Sandrine Madeleine Suzanne Georgeon, Luciano Andres Abriata, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Stéphane Rosset, Eva Anna van Aalen, Leo Scheller

De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structur ...

2021

De novo protein design enables the precise induction of RSV-neutralizing antibodies

Patricia Corthésy Henrioud, Sandrine Madeleine Suzanne Georgeon, Luciano Andres Abriata, Bruno Emanuel Ferreira De Sousa Correia, Elisa Oricchio, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Sabrina Susan Vollers, Mélanie Evelyne Villard, Elie Charles Eugène Dheilly, Stéphane Rosset, Yujia Wang

De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remain ...

American Association for the Advancement of Science2020

Computational design of anti-CRISPR proteins with improved inhibition potency

Wei Sun, Sandrine Madeleine Suzanne Georgeon, Bruno Emanuel Ferreira De Sousa Correia, Zander Harteveld, Andreas Scheck, Stéphane Rosset, Julius Valten Upmeier Zu Belzen, Yujia Wang

Anti-CRISPR (Acr) proteins are powerful tools to control CRISPR-Cas technologies. However, the available Acr repertoire is limited to naturally occurring variants. Here, we applied structure-based design on AcrIIC1, a broad-spectrum CRISPR-Cas9 inhibitor, ...

NATURE PUBLISHING GROUP2020

Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen

Sai Reddy, Patricia Corthésy Henrioud, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Pablo Gainza Cirauqui, Sabrina Susan Vollers, Stéphane Rosset

Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely ...

2019

Rosetta FunFolDes - A general framework for the computational design of functional proteins

Bruno Emanuel Ferreira De Sousa Correia, Anne Marie-Thérèse Suzanne Billet, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Sabrina Susan Vollers, Freyr Sverrisson, Mélanie Evelyne Villard, Andreas Scheck, Sarah Wehrle, Roxanne Marine Lourman, Stéphane Rosset, Karen Schriever

The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function and stability. The low success rates of computational design protocols an ...

2018

Driving Immune Responses with Synthetic Proteins - Development of De Novo Designed Immunogens to Elicit Respiratory Syncytial Virus Neutralizing Antibodies

Patricia Corthésy Henrioud, Bruno Emanuel Ferreira De Sousa Correia, Jaume Bonet Martinez, Fabian Sesterhenn, Che Yang, Stéphane Rosset

WILEY2018