Concept
Allosteric modulator
Publications associées (54)
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 ...
EPFL2024Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization.
Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...
EPFL2024Computational rewiring of allosteric pathways reprograms GPCR selective responses to ligands
Patrick Daniel Barth, Mahdi Hijazi, Aurélien Laurent Jean-Charles Oggier, Dániel Kéri
G-protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and drug targets, and respond to a wide variety of chemical stimuli to activate diverse cellular functions. Understanding and predicting how ligand binding triggers a speci ...
bioRxiv2022Computational design of ultrasensitive flexible peptide:receptor signaling complexes for enhanced chemotaxis
Patrick Daniel Barth, Mahdi Hijazi, Aurélien Laurent Jean-Charles Oggier, Ana Paola Rico Villarreal, Robert Everett Jefferson, Andreas Füglistaler
Engineering biosensors that sensitively recognize specific biomolecules and trigger functional cellular responses is a holy grail of diagnostics and synthetic cell biology. Biosensor design approaches have mostly focused on binding structurally well-define ...
bioRxiv2022Mechanistic Understanding of Neurobehavioral Effects of Insecticides on the Larvae of Zebrafish (Danio rerio)
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 ...
EPFL2022Allosteric 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 PORTFOLIO2021Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design
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 ...
EPFL2021Interfacial 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 SOC2021Novel 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 LTD2021Enhancing the Signaling of GPCRs via Orthosteric Ions
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