Publication
Computationally designed GPCR quaternary structures bias signaling pathway activation
Publications associées (43)
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 ...
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 ...
bioRxiv2022Scaffolding protein functional sites using deep learning
Bruno Emanuel Ferreira De Sousa Correia, Karla Montserrat Castro Gilabert, Basile Isidore Martin Wicky, Jue Wang
The binding and catalytic functions of proteins are generally mediated by a small number of functional residues held in place by the overall protein structure. Here, we describe deep learning approaches for scaffolding such functional sites without needing ...
AMER ASSOC ADVANCEMENT SCIENCE2022Computationally designed GPCR quaternary structures bias signaling pathway activation
Patrick Daniel Barth, Robert Everett Jefferson
Communication across membranes controls critical cellular processes and is achieved by receptors translating extracellular signals into selective cytoplasmic responses. While receptor tertiary structures can now be readily characterized, receptor associati ...
2021Reprogramming 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 ...
EPFL2021Computational design of highly signaling active membrane receptors through de novo solvent-mediated allosteric networks
Jian Wang, Patrick Daniel Barth
Protein catalysis and allostery require the atomic-level orchestration and motion of residues, ligand, solvent and protein effector molecules, but the ability to design protein activity through precise protein-solvent cooperative interactions has not been ...
2021SPServer: split-statistical potentials for the analysis of protein structures and protein-protein interactions
BackgroundStatistical potentials, also named knowledge-based potentials, are scoring functions derived from empirical data that can be used to evaluate the quality of protein folds and protein-protein interaction (PPI) structures. In previous works we deco ...
BMC2021Structural basis of the activation of the CC chemokine receptor 5 by a chemokine agonist
Henning Paul-Julius Stahlberg, Nicolas Calo, Polina Isaikina
The human CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) that plays a major role in inflammation and is involved in cancer, HIV, and COVID-19. Despite its importance as a drug target, the molecular activation mechanism of CCR5, i.e., ...
AMER ASSOC ADVANCEMENT SCIENCE2021Low-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 ...
NATL ACAD SCIENCES2021Functional de novo Protein Design for Targeted Vaccines and Synthetic Biology Applications
Evolution has created, selected and evolved large repertoires of proteins that operate in various biological systems. Nowadays biotechnological needs are coming up orders of magnitude faster than proteins naturally evolve. The emergence of de novo protein ...
EPFL2020