Publications associées à Allosteric modulator

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

Mechanistic Understanding of Neurobehavioral Effects of Insecticides on the Larvae of Zebrafish (Danio rerio)

Sarah-Katharina Könemann

Due to conservation of neuronal functioning across phyla, molecular targets of insecticides are similar in insects and vertebrates. Insecticides thus pose a risk to aquatic vertebrates, such as fish, and potentially cause neurotoxic effects. Although these ...

EPFL2022

Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state

Anne-Marinette Thi Phuong Hanh Cao

Here, the authors use smFRET to assess the structural dynamics of metabotropic glutamate receptor mGlu2 and show that a positive allosteric modulator or the Gi protein stabilize mGlu2 in the glutamate-induced active state, leading to the full activation of ...

Nature Portfolio2021

Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design

Dániel Kéri

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

EPFL2021

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

Frédéric Célerse, Théo Pierre Jaffrelot Inizan

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

Novel irreversible covalent BTK inhibitors discovered using DNA-encoded chemistry

Sevan Mleh Habeshian, Ying Zhang

Libraries of DNA-Encoded small molecules created using combinatorial chemistry and synthetic oligonucleotides are being applied to drug discovery projects across the pharmaceutical industry. The majority of reported projects describe the discovery of rever ...

PERGAMON-ELSEVIER SCIENCE LTD2021

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

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

Computational design of G Protein-Coupled Receptor allosteric signal transductions

Patrick Daniel Barth, Dániel Kéri

Membrane receptors sense and transduce extracellular stimuli into intracellular signaling responses but the molecular underpinnings remain poorly understood. We report a computational approach for designing protein allosteric signaling functions. By combin ...

2020

Mechanics of Allostery: Contrasting the Induced Fit and Population Shift Scenarios

Matthieu Wyart, Solange Marie Flatt, Carolina Brito Carvalho dos Santos, Stefano Zamuner, Riccardo Ravasio

In allosteric proteins, binding a ligand can affect function at a distant location, for example, by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed number of stable c ...

CELL PRESS2019