Publications associées à Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics

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

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

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

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

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

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

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

Landscapes of DNA Mechanics and Genomes

Thomas Antonin Zwahlen

The local physical properties - such as shape and flexibility - of the DNA double-helix is today widely believed to be influenced by nucleic acid sequence in a non-trivial way. Furthermore, there is strong evidence that these properties play a role in many ...

EPFL2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

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

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

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

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

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

First paleoproteome study of fossil fish otoliths and the pristine preservation of the biomineral crystal host

Anders Meibom, Jaroslaw Hubert Stolarski, Jinming Guo

Otoliths are calcium carbonate components of the stato-acoustical organ responsible for hearing and maintenance of the body balance in teleost fish. During their formation, control over, e.g., morphology and carbonate polymorph is influenced by complex ins ...

Nature Portfolio2023

Combining phylogeny and coevolution improves the inference of interaction partners among paralogous proteins

Anne-Florence Raphaëlle Bitbol

Author summaryWhen two protein families interact, their sequences feature statistical dependencies. First, interacting proteins tend to share a common evolutionary history. Second, maintaining structure and interactions through the course of evolution yiel ...

PUBLIC LIBRARY SCIENCE2023

Species-specific regulation of XIST by the JPX/FTX orthologs

Olga Marie Louise Rosspopoff

X chromosome inactivation (XCI) is an essential process, yet it initiates with remarkable diversity in various mammalian species. XIST, the main trigger of XCI, is controlled in the mouse by an interplay of lncRNA genes (LRGs), some of which evolved concom ...

OXFORD UNIV PRESS2023

Towards automating de novo protein design for novel functionalities: controlling protein folds and protein-protein interactions

Zander Harteveld

The sheer size of the protein sequence space is massive: a protein of 100 residues can have 20^100 possible sequence combinations; and knowing that this exceeds the number of atoms in the universe, the chance of randomly discovering a stable new sequence w ...

EPFL2022

Protein language models trained on multiple sequence alignments learn phylogenetic relationships

Umberto Lupo, Anne-Florence Raphaëlle Bitbol, Damiano Sgarbossa

Self-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and AlphaFold's EvoFormer, ...

Nature Portfolio2022

KRAB zinc-finger proteins and their transposable element targets: between antagonism and cooperation

Jonas Caspar De Tribolet-Hardy

There are 377 Krüppel-associated box (KRAB) domain-containing zinc finger proteins (KZFPs) in the human genome, making them the largest family of transcription factors. KZFPs are defined by a N-terminal KRAB domain and several zinc-finger domains arranged ...

EPFL2022

Biological nanopores for single-molecule sensing

Matteo Dal Peraro, Chan Cao, Simon Finn Mayer

Evolution has found countless ways to transport material across cells and cellular compartments separated by membranes. Protein assemblies are the cornerstone for the formation of channels and pores that enable this regulated passage of molecules in and ou ...

2022