Publications associées à A structure-guided fragment-based approach for the discovery of allosteric inhibitors targeting the lipophilic binding site of transcription factor EthR

Chalcogen bonding catalysis

Catalysts play a major role in chemical synthesis, and catalysis is considered to be a green and economic process. Catalysis is dominated by covalent interactions between the catalyst and substrate. The design of non-covalent catalysts came into limelight ...

Royal Society of Chemistry2024

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

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

Elisa Oricchio

We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody-peptide inhibitor conjugates (APICs) that target a family of prot ...

Nature Portfolio2024

Antibodies expand the scope of angiotensin receptor pharmacology

Patrick Daniel Barth, Shuhao Zhang

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often l ...

2024

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

Mechanistic Insight into Supramolecular Polymerization in Water Tunable by Molecular Geometry

Lukas Pfeifer

Supramolecular self-assembly in water based on non-covalent bonding is attracting major attention due to the potential of hydrogels and aqueous polymers in biomedical applications. Although supramolecular polymerization in organic solvents is well establis ...

CHINESE CHEMICAL SOC2022

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

Modeling non-covalent interactions in condensed phase

Veronika Juraskova

The modeling of non-covalent interactions, solvation effects, and chemical reactions in complex molecular environment is a challenging task. Current state-of-the-art approaches often rely on static computations using implicit solvent models and harmonic ap ...

EPFL2022

Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism

Francesco Stellacci, Valeria Cagno, Matteo Gasbarri

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of ...

American Chemical Society2022

Revisiting Cation Complexation and Hydrogen Bonding of Single-Chain Polyguluronate Alginate

Modifying the properties of bio-based materials has garnered increasing interest in recent years. In related applications, the ability of alginates to complex with metal ions has been shown to be effective in liquid-to-gel transitions, useful in the develo ...

American Chemical Society2021

Charge transfer across C-H center dot center dot center dot O hydrogen bonds stabilizes oil droplets in water

Sylvie Roke, Saranya Pullanchery Sankara Narayanan, Sergey Kulik, Benjamin Rehl

The hydrophobic-water interface plays a key role in biological interactions. However, both the hydrophobic-water interfacial molecular structure and the origin of the negative zeta potential of hydrophobic droplets in water are heavily contested. We report ...

American Association for the Advancement of Science2021

Atomic Level Insights of Non-Noble Metal Catalysts for the Oxygen Evolution Reaction

Lichen Bai

The conversion of intermittent renewable energy resources in the form of chemical bond, such as hydrogen production from electrochemical water splitting, is a promising way to satisfy the future global energy demand and address the environmental issues. Th ...

EPFL2021

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

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

Molecular Engineering of Electrode Surfaces for Electrocatalysis

Patrick Eduard Alexa

Electrocatalysts play an important part on the route towards environmental friendly energy sources. They support modern technologies like fuel cells to move further away from the utilization of fossil fuels and the resulting CO2 emission into our atmospher ...

EPFL2020

Hydrogen-Bonded Small Molecules and Polymers in Organic Electronics

Bilal Özen

Organic semiconductors are important components for applications in different fields of technology, as their advantages include the possibility of low-temperature processing as well as low-cost, large-area manufacturing based on solution-based processes, c ...

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

Allosteric Protein Switches based on Antibody Mimetics

Helen Rebecca Ostlund Farrants

Synthetic protein switches are proteins that can be controlled by an external input, and are useful tools to probe protein function. Antibody fragments and antibody mimetics can be selected to bind, activate, or inhibit several diverse protein targets. Nev ...

EPFL2019

Water Activity from Equilibrium Molecular Dynamics Simulations and Kirkwood-Buff Theory

Satoshi Takahama, Mária Lbadaoui-Darvas

Water activity and related thermodynamic properties are calculated for several aqueous solutions using equilibrium molecular dynamics in conjunction with the recent extension of the Kirkwood-Buff (KB) theory for closed systems. The general applicability of ...

AMER CHEMICAL SOC2019

Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling

Yimon Aye, Lingxi Wang

Recent Advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein cysteine, of which there are around 200,000 in the human proteome, and ...

MARY ANN LIEBERT, INC2020