Shuguang Yuan

Shuguang Yuan
Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences · Computer-aided drug discovery research center

Doctor of Philosophy

About

94
Publications
51,501
Reads
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2,878
Citations
Introduction
My research mainly focuses on membrane proteins, especially GPCRs, ion channels, and transporters. Molecular dynamic simulation Drug discovery Molecular modelling
Additional affiliations
April 2019 - present
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Position
  • Professor (Full)
June 2013 - March 2014
École Polytechnique Fédérale de Lausanne
Position
  • PostDoc Position
September 2012 - June 2013
École Polytechnique Fédérale de Lausanne
Position
  • PhD
Education
September 2012 - September 2013
May 2011 - August 2012
Nencki Institute of Experimental Biology, Polish Academy of Science
Field of study
  • GPCR
October 2009 - May 2011
KULeuven University
Field of study
  • biocatalysis

Publications

Publications (94)
Article
Full-text available
Recent crystal structures of G-protein-coupled receptors (GPCRs) have revealed ordered internal water molecules, raising questions about the functional role of those waters for receptor activation that could not be answered by the static structures. Here, we used molecular dynamics simulations to monitor-at atomic and high temporal resolution-confo...
Article
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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, which is especially relevant to GPCRs, concerns ligand selectivity: Why do certain molecules act a...
Article
Full-text available
Identifying a target ligand binding site is an important step for structure-based rational drug design as shown here for G protein-coupled receptors (GPCRs), which are among the most popular drug targets. We applied long-time scale molecular dynamics simulations, coupled with mutagenesis studies, to two prototypical GPCRs, the M3 and M4 muscarinic...
Article
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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 mediated by ORs are unknown. Here, we used molecular modeling, fingerprint interaction analysis...
Article
Full-text available
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 importance for discovering related new medicines. In many GPCRs, an allosteric sodium ion next to the...
Preprint
G-protein coupled receptors (GPCRs) are interesting targets for a broad range of drugs. The comprehensions of the interaction's mode between GPCRs and their ligands remains to be resolved. Here, we present GPCR-IFP, a web server which drives to gather experimental information supports a better understanding of ligand-receptor interaction and the ch...
Article
Full-text available
Neural networks and deep learning have been successfully applied to tackle problems in drug discovery with increasing accuracy over time. There are still many challenges and opportunities to improve molecular property predictions with satisfactory accuracy even further. Here, we proposed a deep-learning architecture model, namely Bidirectional long...
Article
Ketoreductases have shown considerable potential as biocatalysts in the asymmetric synthesis of chiral alcohols. However, compared to the widely studied ketoreductases for chiral alcohols, limited knowledge is available about ketoreductases for efficient dynamic reductive kinetic resolution (DYRKR) of bulky α-amino β-keto esters. In this study, str...
Article
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The Yersinia outer protein J (YopJ) family effectors are widely deployed through the type III secretion system by both plant and animal pathogens. As non-canonical acetyltransferases, the enzymatic activities of YopJ family effectors are allosterically activated by the eukaryote-specific ligand inositol hexaphosphate (InsP6). However, the underpinn...
Article
ketoreductases have shown considerable potentials as biocatalysts in the asymmetric synthesis of chiral alcohols. However, compared to the widely studied ketoreductases for chiral alcohols, limited knowledge is available about ketoreductases for efficient dynamic reductive kinetic resolution (DYRKR) of bulky α-amino β-keto esters. In this study,...
Article
Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It is characterized by reproductive disorders in pregnant sows and respiratory symptoms in pigs of all ages. Although antiviral drugs, vaccines, and improved management have played a role in...
Article
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Staphylococcus xylosus (S. xylosus) has become an emerging opportunistic pathogen due to its strong biofilm formation ability. Simultaneously, the biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Here, we confirmed that rutin can effectively inhibit biofilm formation in S. xylosus, of which the inhibition...
Article
Full-text available
Protein–ligand interaction analysis is important for drug discovery and rational protein design. The existing online tools adopt only a single conformation of the complex structure for calculating and displaying the interactions, whereas both protein residues and ligand molecules are flexible to some extent. The interactions evolved with time in th...
Article
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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. Besides this role, recent studies indicated that metal ions can modulate ligand–GPCR interact...
Preprint
Full-text available
As a result of evolution, certain microbes develop resistance against antimicrobial treatment. The antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of severe infections caused by microbes such as bacteria, viruses, fungi and other parasites. The resistance of Staphylococcus xylosus ( S. xyl...
Article
Engineering of enzymes on the basis of protein structures are rational and efficient approaches to acquire biocatalysts of desired performances. In this study, we focused on a special mono- and diacylglycerol lipase (MDGL) isolated from the lipolytic enzyme-enriched fungus Aspergillus oryzae and discovered improved variants based on its crystal str...
Article
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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 well understood. We report three structures of the Cys-loop 5-HT 3A serotonin receptor (5HT 3...
Article
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Abstract Cutinases could degrade insoluble polyester, including natural cutin and synthetic plastic. However, their turnover efficiency for polyester remains too low for industrial application. Herein, we report the 1.54-Å resolution X-ray crystal structure of a cutinase from Thermobifida fusca and modeling structure in complex with a cutin mimic o...
Article
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An amendment to this paper has been published and can be accessed via the original article.
Article
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The outbreak of COVID-19 by the end of 2019 has posed serious health threats to humanity and jeopardized the global economy. However, no effective drugs are available to treat COVID-19 currently and there is a great demand to fight against it. Here, we combined computational screening and an efficient cellular pseudotyped virus system, confirming t...
Article
Full-text available
Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions, such as inflammation and cancer1. Although ample efforts have been invested into the structural investigation of the chemokine receptors and receptor–chemokine recognition2–4, less is known about endogenous chemo...
Article
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New drug discovery has been acknowledged as a complicated, expensive, time-consuming, and challenging project. It has been estimated that around 12 years and 2.7 billion USD, on average, are demanded for a new drug discovery via traditional drug development pipeline. How to reduce the research cost and speed up the development process of new drug d...
Article
Human endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hindered the development of therapeutic applications. Importantly, missing structural inform...
Article
Full-text available
Adrenergic G-protein-coupled receptors (GPCRs) mediate different cellular signaling pathways in the presence of endogenous catecholamines and play important roles in both physiological and pathological conditions. Extensive studies have been carried out to investigate the structure and function of β adrenergic receptors (βARs). However, the structu...
Article
The cover image is based on the Advanced Review Rationalization of stereoselectivity in enzyme reactions by Shuguang Yuan, Lu Pan, Yi Li, and H. C. Stephen Chan. https://doi.org/10.1002/wcms.1403 Abstract The cover image is based on the Advanced Review Rationalization of stereoselectivity in enzyme reactions by Shuguang Yuan, Lu Pan, Yi Li, and H....
Article
Drug discovery and development are among the most important translational science activities that contribute to human health and well-being. However, the development of a new drug is a very complex, expensive and long process, which typically costs 2.6 billion USD and 12 years on average. How to decrease the costs and speed up new drug discovery ha...
Article
Full-text available
Small self-cleaving ribozymes catalyze site-specific cleavage of their own phosphodiester backbone with implications for viral genome replication, pre-mRNA processing, and alternative splicing. We report on the 2.1-Å crystal structure of the hatchet ribozyme product, which adopts a compact pseudosymmetric dimeric scaffold, with each monomer stabili...
Article
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Linaridins are a small but growing class of natural products belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. The class A linaridins, exemplified by cypemycin, possess an unusual S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) residue. Formation of the AviCys in cypemycin requires an oxidative decarbox...
Article
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 protein-coupled receptors (GPCRs) typically detect extracellular signal molecules on the cell surfa...
Article
Full-text available
SecA is an essential molecular motor for the translocation of proteins across the membrane via the bacterial Sec secretion system. While the Sec system is found in all cells from archaea to multicellular eukaryotes, the SecA protein is mainly found in bacteria. The mechanism of how the motor protein works on a molecular level is still under dispute...
Article
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Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided ap...
Article
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A strategy for rapidly mining biological parts from plants for synthetic biology utilizing natural product-derived chemical probes has been reported.
Article
Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT2C receptor, are useful for treating obesity, drug abuse, and schizophrenia. The competing challenges of developing selective 5-HT2C recep...
Patent
The present invention relates to piperidine derivs. of formula (I) wherein Ar1, Ar2, RAr1, R1, R2, and R3 are as described in the description, their prepn., to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compns. contg. one or more compds. of formula (I) , and esp. to their use as CXCR7 receptor...
Article
Full-text available
Directed evolution of limonene epoxide hydrolase (LEH), which catalyzes the hydrolytic desymmetrization reactions of cyclopentene oxide and cyclohexene oxide, results in (R,R)- and (S,S)-selective mutants. Their crystal structures combined with extensive theoretical computations shed light on the mechanistic intricacies of this widely used enzyme....
Article
Full-text available
GyrI-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 cyclopropanoid cyclopropyl hydrolases (CCHs) that can catalyze the hydrolysis of the potent DNA-alkylating agents yatakemycin (YTM) and CC-1065. Co-crystallography and molecul...
Article
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, especially those acting on the μ-opioid receptor (μOR) and related pathways, have proven to be the mos...
Article
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The possibility of a double Walden inversion mechanism of the fluoracetate dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl acetic acid to the defluorination process. This stereochemical probe led to inversion of configura-tion in a kinetic resolution with an extremely high selectivity factor (E >500), showing that t...
Article
Web browsers have long been recognized as potential platforms for remote macromolecule visualization. However, the difficulty in transferring large-scale data to clients and the lack of native support for hardware-accelerated applications in the local browser undermine the feasibility of such utilities. With the introduction of WebGL and HTML5 tech...
Article
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The cover image, by Shuguang Yuan et al., is based on the Software Focus Using PyMOL as a platform for computational drug design. , DOI: 10.1002/wcms.1298.
Article
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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, and making movies. This Python-based software, alongside many Python plugin tools, has been...
Article
Full-text available
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 been pushing structural biology forward are the remarkable technical advancements that make solv...
Article
Full-text available
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 various physical and chemical stimuli, and prevail as an important target for drug discovery. N...
Article
Full-text available
Effectors secreted by the type III 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 acetylate host proteins and produce virulence. However, the structural basis for this noncanonical a...
Article
Full-text available
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 was used in the NosL reaction, hydrogen abstraction occurs promiscuously at both the amino group...