Publications associées à Characterization of Platinum Anticancer Drug Protein-Binding Sites Using a Top-Down Mass Spectrometric Approach

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

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

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

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

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

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

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

Systematic analysis of biomolecular binding reactions using microfluidic systems

Amir Shahein

Transcription factor binding to a single binding site on DNA and its functional consequence in a promoter context are beginning to be relatively well understood. However, binding to clusters of sites has yet to be characterized in depth, and the functional ...

EPFL2022

Arene-ruthenium(II) complexes with pyrazole-based ligands bearing a pyridine moiety: Synthesis, structure, DFT calculations, and cytotoxicity

Paul Joseph Dyson, Farzaneh Fadaei Tirani, Mouna Hadiji

Two pyrazole-based ligands bearing a pyridine moiety, 3-methyl-1-(pyridin-2-yl)-5-pyrazolone (HLpy), and 3methyl-1-(pyridin-2-yl)-4-trifluoroacetyl-5-pyrazolone (HQpy,CF3), were prepared and fully characterized in the solid-state and the tautomerism of bot ...

ELSEVIER SCIENCE SA2021

Structural and analytical identifications of biomolecules by cold ion spectroscopy of non-covalent complexes

Erik Saparbayev

Non-covalent interactions are ubiquitous in nature. The diversity and functionality of these interactions are employed by nature as a universal tool for building the molecular mechanism of life. Although weak, these interactions play a key role in both for ...

EPFL2021

Low-energy electron holography imaging of conformational variability of single-antibody molecules from electrospray ion beam deposition

Klaus Kern, Stephan Rauschenbach, Sabine Abb, Sven Alexander Szilagyi, Hannah Julia Ochner

Imaging of proteins at the single-molecule level can reveal conformational variability, which is essential for the understanding of biomolecules. To this end, a biologically relevant state of the sample must be retained during both sample preparation and i ...

National Academy of Sciences2021

Interfacial Water Many-Body Effects Drive Structural Dynamics and Allosteric Interactions in SARS-CoV-2 Main Protease Dimerization Interface

Théo Pierre Jaffrelot Inizan, Frédéric Célerse

Following our previous work (Chem. Sci. 2021, 12, 4889-4907), we study the structural dynamics of the SARS-CoV-2 Main Protease dimerization interface (apo dimer) by means of microsecond adaptive sampling molecular dynamics simulations (50 mu s) using the A ...

AMER CHEMICAL SOC2021

Methods for the generation of large combinatorial macrocycle libraries

Sevan Mleh Habeshian

Macrocycles are an attractive class of molecules due to their good binding properties and yet rather small size that allows, in many cases, crossing membranes to reach intracellular targets. In comparison to classical small molecule drugs, macrocycles are ...

EPFL2021

Computational characterisation of the selectivity and binding mode of mono- and binuclear transition metal based anticancer compounds

Thibaud Edouard Alistair von Erlach

The rising resistance and the severe side effects associated with classical anticancer drugs such as cisplatin or mercaptopurines has triggered the development of novel antitumourous agents based on transition metal (e.g. ruthenium, osmium, and gold) organ ...

EPFL2020

Enhancing the Signaling of GPCRs via Orthosteric Ions

Horst Vogel, Shuguang Yuan

G protein-coupled receptors play essential roles in cellular processes such as neuronal signaling, vision, olfaction, tasting, and metabolism. As GPCRs are the most important drug targets, understanding their interactions with ligands is of utmost importan ...

AMER CHEMICAL SOC2020

Statistical physics of interacting proteins: Impact of dataset size and quality assessed in synthetic sequences

Anne-Florence Raphaëlle Bitbol, Pierre Mergny

Identifying protein-protein interactions is crucial for a systems-level understanding of the cell. Recently, algorithms based on inverse statistical physics, e.g., direct coupling analysis (DCA), have allowed to use evolutionarily related sequences to addr ...

2020

Hybrid Transcriptional Regulators for the Screening of Target DNA Motifs in Organohalide-Respiring Bacteria

Christof Holliger, Julien Maillard, Marie Vingerhoets, Mathilde Stéphanie Willemin

The bioremediation of persistent organohalide molecules under anoxic conditions mostly relies on the bacterial process called organohalide respiration (OHR). Organohalide-respiring bacteria (OHRB) are phylogenetically diverse anaerobic bacteria that share ...

Frontiers Media SA2020

Mechanics and co-evolution of allosteric materials and proteins

Riccardo Ravasio

The regulation of several processes inside and outside the cell depends on the action of a particular class of enzymes, called allosteric. In allosteric macromolecules, binding a ligand at one site affects the binding activity at a distal functional site, ...

EPFL2020

Recent Considerations in the Application of RAPTA-C for Cancer Treatment and Perspectives for Its Combination with Immunotherapies

Paul Joseph Dyson, Patrycja Nowak-Sliwinska, Magdalena Rausch

The organometallic ruthenium(II) [Ru(arene)Cl2PTA] PTA - 1,3,5-triaza-7-phosphaadamantane compound, RAPTA-C, represents an innovative anti-cancer therapeutic and a better-tolerated alternative to platinum (Pt)-based chemotherapeutic drugs in the treatment ...

WILEY2019