Publications de Shuguang Yuan | EPFL Graph Search

Computational drug development for membrane protein targets

Henning Paul-Julius Stahlberg, Pierre Vogel, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

2024

Asymmetric opening of the homopentameric 5-HT3A serotonin receptor in lipid bilayers

Horst Vogel, Shuguang Yuan

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout the nervous system. They have been shown to be modulated by the lipid environment, however the underlying mechanism is not ...

Nature Research2021

The role of metal ions in G protein-coupled receptor signalling and drug discovery

Horst Vogel, Shuguang Yuan, Xueying Wang

Metal ions, such as Na+, Mg2+, Ca2+, and Zn2+, are highly abundant in biological systems. For many G protein-coupled receptors (GPCRs), metal ions, especially Na+, have been found to stabilize the receptors' inactivate state preventing receptor activation. ...

WILEY2021

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

Advancing Drug Discovery via Artificial Intelligence

Horst Vogel, Thamani Dahoun, Shuguang Yuan

Drug discovery and development are among the most important translational science activities that contribute to human health and wellbeing. However, the development of a new drug is a very complex, expensive, and long process which typically costs 2.6 bill ...

ELSEVIER SCIENCE LONDON2019

Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compounds

Horst Vogel, Horst Pick, Thamani Dahoun, Shuguang Yuan, Marc Brugarolas Campillos

The mammalian olfactory system uses hundreds of specialized G-protein-coupled olfactory receptors (ORs) to discriminate a nearly unlimited number of odorants. Cognate agonists of most ORs have not yet been identified and potential non-olfactory processes m ...

Springer2019

New Binding Sites, New Opportunities for GPCR Drug Discovery

Horst Vogel, Thamani Dahoun, Shuguang Yuan, Yifan Li, Yen-Huan Li

Many central biological events rely on protein-ligand interactions. The identification and characterization of protein-binding sites for ligands are crucial for the understanding of functions of both endogenous ligands and synthetic drug molecules. G prote ...

ELSEVIER SCIENCE LONDON2019

Exploring a new ligand binding site of G protein-coupled receptors

Horst Vogel, Shuguang Yuan, Junxiong Wang

2018

Designing Safer Analgesics via mu-Opioid Receptor Pathways

Shuguang Yuan, Jianing Li

Pain is both a major clinical and economic problem, affecting more people than diabetes, heart disease, and cancer combined. While a variety of prescribed or over-the-counter (OTC) medications are available for pain management, opioid medications, especial ...

Elsevier Science London2017

Gyrl-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection

Shuguang Yuan, Wei Huang, Yue Yin

Gyrl-like proteins are widely distributed in prokaryotes and eukaryotes, and recognized as small-molecule binding proteins. Here, we identify a subfamily of these proteins as cyclo-propanoid cyclopropyl hydrolases (CCHs) that can catalyze the hydrolysis of ...

Nature Publishing Group2017

Using PyMOL as a platform for computational drug design

Shuguang Yuan, Zhenquan Hu

PyMOL, a cross-platform molecular graphics tool, has been widely used for three-dimensional (3D) visualization of proteins, nucleic acids, small molecules, electron densities, surfaces, and trajectories. It is also capable of editing molecules, ray tracing ...

Wiley2017

The Principles of Ligand Specificity on beta-2-adrenergic receptor

Shuguang Yuan

G protein-coupled receptors are recognized as one of the largest families of membrane proteins. Despite sharing a characteristic seven-transmembrane topology, G protein-coupled receptors regulate a wide range of cellular signaling pathways in response to v ...

Nature Research2016

Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family

Shuguang Yuan

Effectors secreted by the type Ill secretion system are essential for bacterial pathogenesis. Members of the Yersinia outer-protein J (YopJ) family of effectors found in diverse plant and animal pathogens depend on a protease-like catalytic triad to acetyl ...

Nature Publishing Group2016

Mechanistic study of the radical SAM-dependent amine dehydrogenation reactions

Shuguang Yuan, Yue Yin, Qixing Zhang, Xinjian Ji

The radical SAM enzyme NosL catalyzes the conversion of L-Trp to 3-methyl-2-indolic acid, and this reaction is initiated by the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction from the L-Trp amino group. We demonstrate here that when D-Trp wa ...

Royal Society of Chemistry2016

A Gating Mechanism of the Serotonin 5-HT3 Receptor

Horst Vogel, Shuguang Yuan

Our recently solved high-resolution structure of the serotonin 5-HT3 receptor (5-HT3R) delivered the first detailed structural insights for a mammalian pentameric ligand-gated ion channel. Based on this structure, we here performed a total of 2.8-μs all-at ...

Cell Press2016

PyMOL and Inkscape Bridge the Data and the Data Visualization

Horst Vogel, Shuguang Yuan

Structural biology has come a long way, from being a niche interest of specialists to where we are today, with over 127,500 biomolecular structures available in the Protein Data Bank (PDB) as of the writing of this letter. The two main factors that have be ...

Elsevier2016

Mechanistic Studies on the Stereoselectivity of the Serotonin 5-HT1A Receptor

Horst Vogel, Shuguang Yuan

G-protein-coupled receptors (GPCRs) are involved in a wide range of physiological processes, and they have attracted considerable attention as important targets for developing new medicines. A central and largely unresolved question in drug discovery, whic ...

Wiley-Blackwell2016

The Molecular Mechanism of P2Y 1 Receptor Activation

Horst Vogel, Shuguang Yuan

Human purinergic Gprotein-coupled receptor P2Y(1) (P2Y(1)R) is activated by adenosine 5'-diphosphate (ADP) to induce platelet activation and thereby serves as an important antithrombotic drug target. Crystal structures of P2Y(1)R revealed that one ligand ( ...

Wiley-Blackwell2016

The Mechanism of Ligand-Induced Activation or Inhibition of - and -Opioid Receptors

Horst Vogel, Shuguang Yuan

G-protein-coupled receptors (GPCRs) are important targets for treating severe diseases. However why certain molecules act as activators whereas others, with similar structures, block GPCR activation, is poorly understood since the same molecule can activat ...

Wiley-Blackwell2015

W246(6.48) Opens a Gate for a Continuous Intrinsic Water Pathway during Activation of the Adenosine A(2A) Receptor

Horst Vogel, Shuguang Yuan, Zhenquan Hu

The question how G-protein-coupled receptors transduce an extracellular signal by a sequence of transmembrane conformational transitions into an intracellular response remains to be solved at molecular detail. Herein, we use molecular dynamics simulations ...

Wiley-VCH Verlag GmbH2015