Publications related to Macromolecular Symmetric Assembly Prediction Using Swarm Intelligence Dynamic Modeling

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

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

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

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

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

Microsecond time-resolved cryo-electron microscopy

Ulrich Lorenz

Microsecond time-resolved cryo-electron microscopy has emerged as a novel approach for directly observing protein dynamics. By providing microsecond temporal and near-atomic spatial resolution, it has the potential to elucidate a wide range of dynamics tha ...

2024

Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens

Henning Paul-Julius Stahlberg, Dongchun Ni

The synthesis of complex sugars is a key aspect of microbial biology. Cyclic beta-1,2-glucan (C beta G) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). ...

Nature Portfolio2024

Palladium-based supramolecular assemblies: from complex structures to water-soluble anion-receptors

Sylvain Alexandre Marie Sudan

The combination of palladium salts and bipyridyl ligands can lead to the formation of a large variety of coordination complexes, with different shapes and sizes, displaying a very versatile host-guest chemistry. Increasing their structural complexity remai ...

EPFL2024

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

Structural heterogeneity of the ion and lipid channel TMEM16F

Horst Vogel

Transmembrane protein 16 F (TMEM16F) is a Ca2+-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron microscopy (cryo-EM) structures, the mechanism of activation ...

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

Machine learning-aided generative molecular design

Philippe Schwaller, Jeff Guo

Machine learning has provided a means to accelerate early-stage drug discovery by combining molecule generation and filtering steps in a single architecture that leverages the experience and design preferences of medicinal chemists. However, designing mach ...

Nature Portfolio2024

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

Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis

Andreas Füglistaler, Aurélien Laurent Jean-Charles Oggier, Mahdi Hijazi, Patrick Daniel Barth, Robert Everett Jefferson, Ana Paola Rico Villarreal

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well ...

Nature Research2023

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

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

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

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 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