About

Academic Experiences

Dr Shuguang Yuan obtained his master degree in organic chemistry, biochemistry and structural biology from the Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences in 2009. Following that, his doctoral dissertation was funded by the Maria Curia Fellowship. It was conducted in three different institutes in Europe: EPFL(Switzerland),Polish Academy of Science(Poland) and KULeuven University(Belgium). In his research, he investigated the principles of various biological systems including enzymes, kinases, ion channels, transporters and, in particular, G protein-coupled receptors (GPCRs). In June 2013, he was awarded with a PhD title with the honor of distinguished thesis. Following that, he was offered the Marie Curie ETH Postdoc Fellowship. In 2014, Dr. Yuan proposed the activation mechanism and the continuous water channel of GPCRs (Nature Communications, 2014), which are widely recognized in this area. In the past few years, he has advanced two of his designed molecules into clinical trials. In 2016, he was invited to join the editorial board of the Journal of Bioinformatics, Computational and Systems Biology. In 2018, he was honored with a title of “affiliate professor” by the University of Warsaw.

Research Scopes

Currently, Dr. Shuguang Yuan is focused on the signalling mechanism and computer aided drug discovery (CADD) of G protein-coupled receptors (GPCRs). GPCRs regulate central human physiological responses to neurotransmitters, hormones, and environmental stimuli, and are among the most important therapeutic targets for many diseases including diabetes, pain, cancer, Alzheimer's disease and so on. About 40% of all marketed medicines are targeting GPCRs. Besides that, he is also interested in investigating enzyme catalytic mechanisms and enzyme engineerings. Furthermore, ligand-gated ion channels, transporters, kinase and disordered proteins are also within his research scopes. Dr. Yuan wishes that his work can benefit the entire human health exensively.

Research network

Dr. Shuguang Yuan has established an extensively international collaboration network in the area of structural biology, biochemistry and medicinal chemistry. These include the University of Southern California, iHuman Institute of the ShanghaiTech Unviersity, Case Western Reserve University, Swiss Federal Institute of Technology Lausanne (EPFL), University of California Los Angeles(UCLA), Max-Planck Institute, University of Copenhagen, Shanghai Institute of Organic Chenistry (SIOC, CAS), Fudan University, to name a few. Dr. Shuguang Yuan is involved in the GPCR Glisten network. He has also established extensive industrial network for drug discovery.

Publications

* corresponding authors #joint first authors

2018
(30) Patent: Aissaoui H., Guerry P., Lehembre F., Pothier J., Pouzol L., Richard S., Yuan S., Piperidine CXCR7 receptor modulators. (2018). (patent no. WO 2018/019929 A1)

(29) Peng Y., McCorvy J., Harpsøe K., Lansu K, Yuan S., et. al. Roth B.*, Stevens R.*, Liu Z.*, 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology. Cell (2018). (doi:10.1016/j.cell.2018.01.001, IF=30.4)

2017
(28) Sun Z., Wu L., Bocola M., Chan H.C., Lonsdale R., Kong X., Yuan S.*, Zhou J.*, Reetz M.*, Structural and Computational Insight into the Catalytic Mechanism of Limonene Epoxide Hydrolase Mutants in Stereoselective Transformations. Journal of the American Chemical Society (2017). (doi:10.1021/jacs.7b10278, IF=13.9)

(27) Yuan H., Zhang J., Cai Y., Wu S., Yang K., Chan S., Huang W., Jin W., Li Y., Yin Y., Igarashi Y., Yuan S.*, Zhou J.*, Tang G.*, GyrI-like proteins catalyze cyclopropanoid hydrolysis to confer cellular protection. Nature communications (2017). (doi:10.1038/s41467-017-01508-1, IF=12.1)

(26) Chan H.C., McCarthy D., Li J., Palczewski K., Yuan S.*, Designing Safer Analgesics via µ-Opioid Receptor Pathways. Trends in Pharmacological Sciences (2017). (doi:10.1016/j.tips.2017.08.004, IF=12.8)

(25) Wang J., Llie A., Yuan S.*, Reetz M.*, Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a Stereochemical Probe. Journal of the American Chemical Society (2017). (doi:10.1021/jacs.7b06019, IF=13.9)

(24) Yuan S.*, Chan H.C., Hu Z.Q., Implementing WebGL and HTML5 in macromolecular visualization and modern computer-aided drug design. Trends in Biotechnology (2017).(doi:10.1016/j.tibtech.2017.03.009, IF=11.1)

(23) Yuan S.*, Chan H.C., Hu Z.Q.,Using PyMOL as a platform for computational drug design. Computational Molecular Science, doi:10.1002/wcms.1298 (2017). (cover story, doi:10.1002/wcms.1303, IF=14.0)

2016
(22) Yuan S.*, Peng Q., Palczewski K., Vogel H., Filipek S*. Mechanistic Studies on the Stereoselectivity of the Serotonin 5-HT1A Receptor. Angewandte Chemie Int Ed Engl 55, 8661-8665, doi:10.1002/anie.201603766 (2016). (IF=12.0)

(21) Yuan S.*, Chan H. C., Vogel H., Filipek S., Stevens R.C.*, Palczewski, K*. The Molecular Mechanism of P2Y1 Receptor Activation. Angewandte Chemie Int Ed Engl 55, 10331-10335, doi:10.1002/anie.201605147 (2016). (IF=12.0)

(20) Zhang Z, Ma K., Yuan S., Luo Y., Jiang S., Hawara E., Pan S., Ma W.* Song, J*. Structure of a pathogen effector reveals the enzymatic mechanism of a novel acetyltransferase family. Nature structural & molecular biology, doi:10.1038/nsmb.3279 (2016). (IF=12.6)

(19) Yuan S.*, Chan H.C., Filipek S., Vogel H., PyMOL and Inkscape bridge the data and the data visualization. Structure, doi:10.1016/j.str.2016.11.012 (2016). (IF=4.9)

(18) Chan H. C., Filipek S.*, Yuan S.*, The Principles of Ligand Specificity on beta-2-adrenergic receptor. Scientific Reports, doi:10.1038/srep34736 (2016). (IF=4.2)

(17) Yuan S.*, Filipek S., Vogel*, H. A Gating Mechanism of the Serotonin 5-HT3 Receptor. Structure 24, 816-825, doi:10.1016/j.str.2016.03.019 (2016). (IF=4.9)

(16) Ji X., Liu W., Yuan S., Ding W.*, Zhang Q*. Mechanistic study of the radical SAM-dependent amine dehydrogenation reactions. Chemical Communications, doi: 10.1039/C6CC05661J (2016). (IF=6.3)

2015
(15) Yuan S.*, Palczewski K., Peng Q., Kolinski M., Vogel H., Filipek S*. The Mechanism of Ligand-Induced Activation or Inhibition of mu- and kappa-Opioid Receptors. Angewandte Chemie Int Ed Engl 54, 7560-7563, doi:10.1002/anie.201501742 (2015). (VIP paper IF=12.0)

(14) Baud O., Yuan S., Veya L., Filipek S., Vogel H*., Pick H*. Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles. Scientific Reports 5, 14948, doi:10.1038/srep14948 (2015). (IF=4.2)

2014
(13) Yuan S.*, Hu Z., Filipek S., Vogel H*. W246 Opens a Gate for a Continuous Intrinsic Water Pathway during Activation of the Adenosine A Receptor. Angewandte Chemie Int Ed Engl 54, 556-559, doi:10.1002/anie.201409679 (2014). (IF=12.0)

(12) Yuan S.*, Filipek S., Palczewski K., Vogel H*. Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway. Nature communications 5, 4733, doi:10.1038/ncomms5733 (2014). (IF=12.1)

(11) Kong X, Yuan S., Li L., Chen S., Xu J. H., Zhou J* . Engineering of an epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates. Proc Natl Acad Sci U S A 111, 15717-15722, doi:10.1073/pnas.1404915111 (2014). (IF=9.6)

(10) Kufareva I., Katritch V., Participants of GPCR contests, Stevens R. C., Abagyan R* . Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. Structure 22, 1120-1139, doi:10.1016/j.str.2014.06.012 (2014). (IF=4.9)

2013
(9) Yuan S.*, Vogel H., Filipek S*. The Role of Water and Sodium Ions in the Activation of the mu-Opioid Receptor. Angewandte Chemie Int Ed Engl 52, 10112-10115, doi:10.1002/anie.201302244 (2013). (IF=12.0)

(8) Yuan S.*, Wu R., Latek D., Trzaskowski B., Filipek S*. Lipid Receptor S1P1 Activation Scheme Concluded from Microsecond All-Atom Molecular Dynamics Simulations. PLoS Computational Biolology 9, e1003261, doi:10.1371/journal.pcbi.1003261 (2013). (IF=4.5)

(7) Wu Y., Yuan S., Chen S., Wu D., Chen J., Wu J*. Enhancing the production of galacto-oligosaccharides by mutagenesis of Sulfolobus solfataricus beta-galactosidase. Food chemistry 138, 1588-1595, doi:10.1016/j.foodchem.2012.11.052 (2013). (IF=4.5)

(6) Le Roy K., Vergauwen R., Struyf T., Yuan S., Lammens W., Matrai J., De Maeyer M., Van den Ende W*. Understanding the role of defective invertases in plants: tobacco Nin88 fails to degrade sucrose. Plant physiology 161, 1670-1681, doi:10.1104/pp.112.209460 (2013). (IF=6.5)

before 2013
(5) Yuan S., Le Roy K., Venken T., Lammens W., Van den Ende W., De Maeyer M*. pKa modulation of the acid/base catalyst within GH32 and GH68: a role in substrate/inhibitor specificity? PloS one 7, e37453, doi:10.1371/journal.pone.0037453 (2012). (IF=2.8)

(4) Yuan S., Ghoshdastider U., Trzaskowski B., Latek D., Debinski A., Pulawski W., Wu R., Gerke V., Filipek*, S. The role of water in activation mechanism of human N-formyl peptide receptor 1 (FPR1) based on molecular dynamics simulations. PloS one 7, e47114, doi:10.1371/journal.pone.0047114 (2012). (IF=2.8)

(3) Trzaskowski B., Latek D., Yuan S., Ghoshdastider U., Debinski A., Filipek S*. Action of molecular switches in GPCRs - theoretical and experimental studies. Curr Med Chem 19, 1090-1109 (2012). (IF=3.2)

(2) Lammens W., Le Roy K., Yuan S., Vergauwen R., Rabijns A., Van Laere A., Strelkov S. V., Van den Ende W*. Crystal structure of 6-SST/6-SFT from Pachysandra terminalis, a plant fructan biosynthesizing enzyme in complex with its acceptor substrate 6-kestose. The Plant journal : for cell and molecular biology 70, 205-219, doi:10.1111/j.1365-313X.2011.04858.x (2012). (IF=5.9)

(1) Zheng C., Liu H. H., Yuan S., Zhou J., Zhang B*. Molecular basis of LMAN1 in coordinating LMAN1-MCFD2 cargo receptor formation and ER-to-Golgi transport of FV/FVIII. Blood 116, 5698-5706, doi:10.1182/blood-2010-04-278325 (2010). (IF=13.1)

News

New publications

Scientific Works Dr. Shuguang Yuan 14, December 2017

Dr. Yuan has found a new catalytic binding site for enzyme CCH which is different from the one observed in the crystal structure. This result was confirmed by subsequent mutagenesis study. Dr. Yuan also captured the substrate entrance pathway and product leaving pathway, using metaMD simulations. A catalytic mechanism was proposed for CCH by Dr. Yuan. This work was published in Nature Communications (doi:10.1038/s41467-017-01508-1) recenntly. Besides that, Dr. Yuan introudced quantum mechanics (QM), as well as molecular dynamics (MD) simulations, to reveal the stereoselectivity of enzyme LEH. A catalytic mechanism was also proposed by Dr. Yuan. This work was published in JACS (doi:10.1021/jacs.7b10278) recently.
read more

The 15th Annual Congress of International Drug Discovery Science and Technology

invited talk Dr. Shuguang Yuan 25-27 July 2017, Osaka, Japan

Dr. Shuguang Yuan is invited to the 15th Annual Congress of International Drug Discovery Science and Technology - Japan 2017 (IDDST-Japan 2017) with theme “Dedicated to Accelerating Drug Innovation 1\007. He will give a talk on "The ligand stereoselectivity of the serotonin 5-HT1A receptor."
read more

Cold Spring Harbor Conference on membrane protein

invited talk Dr. Shuguang Yuan May 15-19 2017, Suzhou, China

Dr. Yuan has been invited to the Cold Spring Harbor Conference on membrane protein. He will give a talk on a successful story of odorant receptor drug discovery.

Highlighted work

Scientific news Dr. Shuguang Yuan April 20 2017

Our work on PyMOL and Computer-Aided Drug Discovery (CADD) appeals to a broad scientific audience. It has been highlighted in the Wiley Advanced Science News.

Dr. Yuan has invited Prof. Zhijie Liu to Basel for a scientific talk on GPCR research

Scientific network Dr. Shuguang Yuan March 20 2017, Basel, Switzerland

Prof. Zhijie Liu, the deputy director of the iHuman Institute at the ShanghaiTech Unviersity, has been invited by Dr. Yuan to Basel for a sceintific talk on the latest progesses of GPCR research.
read more

A cover story is selected by the WIREs Computational Molecular Science

Publication Dr. Shuguang Yuan Feb 2017,Wiley Online Library

The publication (doi:10.1002/wcms.1298) entitled "Using PyMOL as a platform for computational drug design" has been selected as a cover story (doi:10.1002/wcms.1303)for WIREs Computational Molecular Science. It would be published online in February, 2017
read more

The 4th annual Shanghai iHuman Forum

invited talk Dr. Shuguang Yuan 5-6 November 2016, Shanghai, China

Dr. Shuguang Yuan is invited by Prof. Raymond C Stevens to the 4th anuual Shanghai iHuman Forum. He will deliver a talk on the "Principle of GPCRs ligand specificities"
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GPCRs Activation

GPCR signalling

Protein-ligand interaction

Rational drug design

Enzyme catalysis