Publications associées à H-1, C-13 and N-15 assignment of the C-terminal domain of GNA2132 from Neisseria meningitidis

Opportunities and challenges in design and optimization of protein function

Bruno Emanuel Ferreira De Sousa Correia, Casper Alexander Goverde

The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calcu ...

Nature Portfolio2024

Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations

Felix Naef, Pierre Vandergheynst, Cédric Gobet, Mohan Vamsi Nallapareddy, Francesco Craighero

Translation elongation plays an important role in regulating protein concentrations in the cell, and dysregulation of this process has been linked to several human diseases. In this study, we use data from ribo-seq experiments to model ribosome densities, ...

PMLR2024

Predicting protein interactions using geometric deep learning on protein surfaces

Freyr Sverrisson

In the domain of computational structural biology, predicting protein interactions based on molecular structure remains a pivotal challenge. This thesis delves into this challenge through a series of interconnected studies. The first chapter introduces th ...

EPFL2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Zhidian Zhang

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

EPFL2024

Microsecond Time-Resolved Cryo-Electron Microscopy

Oliver Florian Harder

Recently, single-particle cryo-electron microscopy emerged as a technique capable of determining protein structures at near-atomic resolution and resolving protein dynamics with a temporal resolution ranging from second to milliseconds. This thesis describ ...

EPFL2024

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Anthony Marchand

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

EPFL2024

Mechanisms and functions of protein S-acylation

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Francisco De Magalhães Sarmento R De Mesquita

Over the past two decades, protein S-acylation (often referred to as S-palmitoylation) has emerged as an important regulator of vital signalling pathways. S-Acylation is a reversible post-translational modification that involves the attachment of a fatty a ...

Nature Portfolio2024

Development of tools and methods for protein identification: From single molecules to in vivo applications

Salome Riccarda Püntener

As the fundamental machinery orchestrating cellular functions, proteins influence the state of every cell profoundly. As cells exhibit significant variations from one to another, analyzing the proteome on a single-cell level is imperative to unravel their ...

EPFL2024

Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Hydrostatic Pressure Stimuli

Yanheng Guo

Cartilage homeostasis, crucial for musculoskeletal function, is orchestrated by interconnected biophysical cues. In healthy cartilage, repetitive compressive loading not only elicits a range of mechanical stimuli but also induces a gradual transient temper ...

EPFL2024

Recording physiological history of cells with chemical labeling

Kai Johnsson, Julien Hiblot, Ling Hai

Recordings of the physiological history of cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce a method to record transient cellular events for later analysis. We designed proteins t ...

American Association for the Advancement of Science2024

Benchmarking machine-readable vectors of chemical reactions on computed activation barriers

Anne-Clémence Corminboeuf, Yannick Calvino Alonso, Puck Elisabeth van Gerwen, Ksenia Briling, Malte Martin Franke

In recent years, there has been a surge of interest in predicting computed activation barriers, to enable the acceleration of the automated exploration of reaction networks. Consequently, various predictive approaches have emerged, ranging from graph-based ...

Royal Soc Chemistry2024

Ion Spectroscopy Reveals Structural Difference for Proteins Microhydrated by Retention and Condensation of Water

Oleg Boyarkine, Andrei Zviagin

Protein ubiquitin in its +7 charge state microhydrated by 5 and 10 water molecules has been interrogated in the gas phase by cold ion UV/IR spectroscopy. The complexes were formed either by condensing water onto the unfolded bare proteins in a temperature- ...

Amer Chemical Soc2024

A new age in protein design empowered by deep learning

Bruno Emanuel Ferreira De Sousa Correia, Michael Bronstein, Casper Alexander Goverde, Ilia Igashov, Arne Schneuing, Hamed Khakzad

The rapid progress in the field of deep learning has had a significant impact on protein design. Deep learning methods have recently produced a breakthrough in protein structure prediction, leading to the availability of high-quality models for millions of ...

Cell Press2023

Generative power of a protein language model trained on multiple sequence alignments

Umberto Lupo, Anne-Florence Raphaëlle Bitbol, Damiano Sgarbossa

Computational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility for generating no ...

eLIFE SCIENCES PUBL LTD2023

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

De novo designed proteins: a study in engineering novel folds and functions

Alexandra Krina Van Hall-Beauvais

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

EPFL2023

A Geometric Transformer for Structural Biology: Development and Applications of the Protein Structure Transformer

Lucien Fabrice Krapp

Proteins, the central building blocks of life, play pivotal roles in nearly every biological function. To do so, these macromolecular structures interact with their surrounding environment in complex ways, leading to diverse functional behaviors. The predi ...

EPFL2023

Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins

Ghérici Hassaïne

Scaffold-based protein libraries are designed to be both diverse and rich in functional/folded proteins. However, introducing an extended diversity while preserving stability of the initial scaffold remains a challenge. Here we developed an original approa ...

Nature Portfolio2023

Secondary structure of the human mitochondrial genome affects formation of deletions

Jacques Fellay, Konstantin Popadin

BackgroundAging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain ...

BMC2023