Publications associées à Short linear motif

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

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

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

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

Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies

Henning Paul-Julius Stahlberg, Dongchun Ni

ABCG2 is an ATP-binding cassette transporter that exports a wide range of xenobiotic compounds and has been recognized as a contributing factor for multidrug resistance in cancer cells. Substrate and inhibitor interactions with ABCG2 have been extensively ...

Academic Press Ltd- Elsevier Science Ltd2023

Systems and methods for de novo design of protein interactions with learned surface fingerprints

Andreas Scheck, Michael Bronstein, Anthony Marchand, Pablo Gainza Cirauqui, Zander Harteveld, Sarah Wehrle, Freyr Sverrisson, Alexandra Krina Van Hall-Beauvais

The present application relates to a computer-implemented systems and methods for protein interaction design using surface fingerprints. The method comprises predicting at least one target interface site with high binding propensity, wherein, optionally, t ...

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

TiCl3-Mediated Reductive Cyclization of Tetrasubstituted Alkenes and Enol Esters Bearing a 2-Nitrophenyl Substituent

Dina Boyarskaya

Indole is one of the most important heterocycles widely present in bioactive natural products, pharmaceuticals, agrochemicals and materials. Being easily accessible, the 2-nitrostyrenes are attractive starting materials for the indole synthesis and the Cad ...

EPFL2023

Multivalent Virucidal Antivirals: Synthesis, Mechanisms of Action, and Immune-stimulating Effects

Yong Zhu

Viruses initiate invasion by binding to cell surface glycoproteins. Materials mimicking the carbohydrate motifs of these glycoproteins, such as heparan sulfate (HS) and sialic acid (SA) can block viral attachment and inhibit the infection. Multivalent disp ...

EPFL2023

Supramolecular Polymer Brushes

Friederike Katharina Metze

Thin polymer coatings present a method to modify the surface properties of underlying substrates. Polymer-coated surfaces have been used as anticorrosive materials, surfaces with special wetting properties, antifriction materials, and as materials for biom ...

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

Two-Carbon Ring Expansion of Cyclobutanols to Cyclohexenones Enabled by Indole Radical Cation Intermediate: Development and Application to a Total Synthesis of Uleine

Qian Wang, Jieping Zhu, Alexandre Julien Florent Leclair

A single-electron transfer (SET) oxidation of indole or benzo[b]thiophene to a radical cation reverses the intrinsic polarity of these pi-excessive bicyclic heteroarenes. Here we report an oxidative two-carbon homologation of cyclobutanols to cyclohexenone ...

AMER CHEMICAL SOC2022

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

Computational design of novel protein–protein interactions – An overview on methodological approaches and applications

Bruno Emanuel Ferreira De Sousa Correia, Anthony Marchand, Alexandra Krina Van Hall-Beauvais

Protein–protein interactions (PPIs) govern numerous cellular functions in terms of signaling, transport, defense and many others. Designing novel PPIs poses a fundamental challenge to our understanding of molecular interactions. The capability to robustly ...

2022

Structure-Property Relationships in Complex Materials by Combining Supervised and Unsupervised Machine Learning

Benjamin Aaron Helfrecht

The work presented in this thesis combines supervised and unsupervised machine learning to examine structure-property relationships in databases of materials. While either supervised learning or unsupervised learning alone can be a powerful tool for assess ...

EPFL2021

The Nt17 Domain and its Helical Conformation Regulate the Aggregation, Cellular Properties and Neurotoxicity of Mutant Huntingtin Exon 1

Giovanni Dietler, Hilal Lashuel, Anne-Laure Mahul Mellier, Francesco Simone Ruggeri, Anass Chiki, Sean Michael Deguire, Urszula Beata Cendrowska, Sophie Vieweg, Nathan Alain Denis Riguet

Converging evidence points to the N-terminal domain comprising the first 17 amino acids of the Huntingtin protein (Nt17) as a key regulator of its aggregation, cellular properties and toxicity. In this study, we further investigated the interplay between N ...

Elsevier2021

Similarities and Differences among Protein Dynamics Studied by Variable Temperature Nuclear Magnetic Resonance Relaxation

David Lyndon Emsley, Jayasubba Reddy Yarava, Andrea Bertarello, Baptiste Busi, François Freymond

Understanding and describing the dynamics of proteins is one of the major challenges in biology. Here, we use multifield variable-temperature NMR longitudinal relaxation (R-1) measurements to determine the hierarchical activation energies of motions of fou ...

AMER CHEMICAL SOC2021

Homoeolog Inference Methods Requiring Bidirectional Best Hits or Synteny Miss Many Pairs

Shaoline Sheppard

Homoeologs are pairs of genes or chromosomes in the same species that originated by speciation and were brought back together in the same genome by allopolyploidization. Bioinformatic methods for accurate homoeology inference are crucial for studying the e ...

OXFORD UNIV PRESS2021

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

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

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

MPGM: Scalable and Accurate Multiple Network Alignment

Matthias Grossglauser, Ehsan Kazemi

Protein-protein interaction (PPI) network alignment is a canonical operation to transfer biological knowledge among species. The alignment of PPI-networks has many applications, such as the prediction of protein function, detection of conserved network mot ...

IEEE COMPUTER SOC2020

Clofarabine Commandeers the RNR-alpha-ZRANB3 Nuclear Signaling Axis

Yimon Aye, Yi Zhao

Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...

CELL PRESS2020