Shuguang Zhang is at MIT Media Lab, Massachusetts Institute of Technology. His current research focuses on designs of biological molecules, particularly proteins and peptides.  He received his B.S from Sichuan University, China and Ph.D. in Biochemistry & Molecular Biology from University of California at Santa Barbara, USA. He was an American Cancer Society Postdoctoral Fellow and a Whitaker Foundation Investigator at MIT. He was a 2003 Fellow of Japan Society for Promotion of Science (JSPS fellow). His work of designer self-assembling peptide scaffold won 2004 R&D100 award. He won a 2006 Guggenheim Fellowship and spent academic sabbatical in University of Cambridge, Cambridge, UK.  He won 2006 Wilhelm Exner Medal of Austria. He was elected to Austrian Academy of Sciences in 2010. He was elected to American Institute of Medical and Biological Engineering in 2011 and elected to US National Academy of Inventors in 2013, and elected to the European Academy of Science and Arts in 2021. He won the 2020 Emil Thomas Kaiser Award from the Protein Society.  He is a honorary member of the Erwin Schrodinger Society and gave for the 20th Erwin Schrödinger Colloquium at the Austrian Academy of Sciences in 2021. He published over 200 scientific papers that have been cited over 36,600 with a h-index 91. He is also a board member of Molecular Frontiers Foundation.  Molecular Frontiers Foundation organizes annually Molecular Frontiers Symposia in Sweden and around the world. The Foundation encourages young people to ask big and good scientific questions about nature. The selected winners will be awarded for Molecular Frontiers Inquiry Prize.

Shuguang Zhang made a serendipitous discovery of a repetitious and ionic self-complementary peptide segment in yeast protein Zuotin in 1990. This is the discovery of the first self-assembling peptides that eventually led to the development of a new field of peptide nanobiotecnology.  Furthermore, his discovery inspired numerous people around the world to design a variety of self-assembling peptides for widespread uses including peptide hydrogels in materials science, 3D tissue cell culture, 3D tissue printing and tissue engineering, nanomedicine, sustained molecular releases, clinical and surgical applications.  He co-founded a startup company that has made significant contributions to bring the self-assembling peptide materials to human clinical and surgical use. He founded a biotech company 3-D Matrix in 2002 that went to IPO in October 2011. It had a US$1 billion market capitalization in 2013.

Shuguang Zhang in 2011 conceived the QTY code to design membrane proteins because there are ~26% genes that code for membrane proteins in human genomes which are crucial for both internal and external cellular communications.  The QTY code is a simple molecular code: namely, glutamine (Q), Threonine (T) and Tyrosine (Y) systematically replace the hydrophobic amino acids Leucine (L), Valine (V), Isoleucine (I), and Phenylalanine (F) in the transmembrane a-helices of membrane proteins including G protein-coupled receptors (GPCRs).  GPCRs function similar like our mobile phones to communicate and interact with external world. The QTY code results suggest that despite 46%-56% transmembrane a-helices changes, water-soluble QTY variants still maintain stable structures and biological function, namely, ligand-binding activities. This simple QTY code is a likely useful tool and has big impact for designs of water-soluble variants of previously water-insoluble glucose transporters, solute carrier transporters, ABC transporters, ion channels, voltage-gated ion channels, and perhaps aggregated proteins including amyloids.

 The QTY code is based on two key molecular structural facts: 1) all 20 amino acids are found in natural alpha-helices regardless of their chemical properties; 2) several amino acids share striking structural similarities despite their very different chemical properties; for example, glutamine (Q) vs Leucine (L); Threonine (T) vs Valine (V) and Isoleucine (I); and Tyrosine (Y) vs Phenylalanine (F).  Despite substantial transmembrane domain changes, the QTY variants maintain stable structures and ligand-binding activities. Zhang’s lab has been successful in designing water-soluble variants of membrane proteins. The AphlaFold2 predictions and experiments performed by others proved the QTY code validity.

Furthermore, recently during large gene library synthesis and due to an imperfect DNA assembly (a technical mistake), he made an unexpected discovery in 2014 that some non-full-length membrane receptors can still bind their natural ligands.  This discovery has far reaching implications for the so-called pseudo-genes in genomes.  Some of such pseudo-genes may code for non-full-length proteins that may still be involved in biological regulations. Similar to microRNA, this discovery may alert scientists to carefully study the overlooked widespread pseudo-genes in genomes.

Recent scientific publications on the QTY code:

Zhang, S., Tao, F., Qing, R., Tang, H., Skuhersky, M., Corin, K., Tegler, L., Wassie, A., Wassie, B., Kwon, Y., Suter, B., Schubert, T., Yang, G., Labahn, J., Kubicek J., & Maertens, B. (2018) QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities. Proc. Natl. Acad. Sci. USA 115 (37) E8652-E8659.

Qing, R., Han, Q., Fei, T., Skuhersky, M., Badr, M., Chung, H., Schubert, T., & Zhang, S. (2019) QTY code designed thermostable and water-soluble chimeric chemokine receptors with tunable ligand-binding activities. Proc. Natl. Acad. Sci. USA 116 (51) 25668-25676.

Hao, SL., Jin D., Zhang, S. & Qing, R. (2020) QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands. QRB Discovery 1 (e4) 1-9, Cambridge University Press

Qing, R., Tao, F., Han, Q., Chung, H., Ni, J., Suter, B., Kubicek, J., Maertens, B., Schubert, T. & Zhang, S. (2020) Non-full-length water-soluble CXCR4QTY, CCR5QTY chemokine receptors and implication for overlooked truncated membrane receptors iScience, Cell Press, 23 (12): 101670.

Tegler, L.T., Corin, K., Skuhersky, M., Pick, H. Vogel, H. & Zhang, S. (2020) G protein-coupled receptor CXCR4 designed by the QTY code becomes more hydrophilic and retains cell-signaling activity. Scientific Reports UK 10, 21371.

Skuhersky, M., Tao, F., Qing, R., Smorodina, E., Jin, D., & Zhang, S. (2021) Comparing native crystal structures and AlphaFold2 predicted water-soluble G protein-coupled receptor QTY variants. Life 11(12) 10.3390/life11121285

Tao, F., Tang, H., Zhang, S. Li, M., & Xu, P. (2022) Enabling QTY server for designing water-soluble α-helical transmembrane proteins. MBio 13 (1) e03604-21 https://doi.org/10.1128/mbio.03604-21

Smorodina, E., Tao, F., Qing, R., Jin, D., Yang, S. & Zhang, S. (2022) Comparing 2 crystal structures and 12 AlphaFold2 predicted human membrane glucose transporters and their water-soluble QTY variants. QRB Discovery 3, e5, 1-11.

Smorodina, E., Igor Diankin, Tao, F., Qing, R., Yang, S. & Zhang, S. (2022) Structural informatic study of determined and AlphaFold2 predicted molecular structures of 13 human solute carrier transporters and their water-soluble QTY variants. Scientific Reports 12, 20103. doi: 10.1038/s41598-022-23764-y.

Egli, M. & Zhang, S. (2022) How the alpha-helix got its name. Nat Rev Mol Cell Biol. 23, 165.

Zhang, S. & Egli, M. (2022) Hiding in plain sight: three chemically distinct α-helix types. Quarterly Review of Biophysics (QRB) 55, e7. 

Qing, R., Hao, S.L., Smorodina, E, Zalevsky, A., Jin, D. & Zhang, S. (2022) Protein design: from the aspect of water solubility. Chemical Reviews, 122, 18, 14085-14179.

Zhang, S. (2022) Life has its ups and downs, always ask questions. Molecular Frontiers Journal, Vol. 6, No. 01n02.

Qing, R., Xue, M., Zhao, J., Wu, L., Breitwieser, A., Smorodina, E., Schubert, T., Azzellino, G., Jin, D., Kong, J., Palacios, T., Sleytr, U.B. & Zhang, S. (2023) Scalable biomimetic sensing system with membrane receptor dual-monolayer probe and graphene transistor arrays. Sci. Advances 9,, eadf1402 (21 July 2023).

Meng, R., Hao, S., Sun, C., Hou, Z., Hou, Y., Wang, L., Deng, P., Deng, J., Yang, Y., Xia, H., Wang, B., Qing, R. & Zhang, S. (2023) Reverse-QTY code design of active human serum albumin self-assembled amphiphilic nanoparticles for effective anti-tumor drug doxorubicin release in mice. PNAS, Vol. 120, No. 21, e220173120, May 15, 2023. https://doi.org/10.1073/pnas.2220173120.

Smorodina, E., Tao, F., Qing, R., Yang, S. & Zhang, S. (2023) Structural bioinformatics of molecular structures of 6 determined and 12 AlphaFold2 predicted native human potassium channels and their water-soluble QTY variants. Scientific Reports (2023).

Akash Sajeef-Sheeja, Eva Smorodina, & Shuguang Zhang. (2023) Structural bioinformatics studies of bacterial beta barrel transporters and their AlphaFold2 predicted water-soluble QTY variants PLOS One (August 22, 2023), https://doi.org/10.1371/journal.pone.0290360.

Mengke Li, Yanze Wang, Fei Tao, Ping Xu, Shuguang Zhang. (2023) QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study. Proteins 92:2 (First published: 05 October 2023). https://doi.org/10.1002/prot.26603.

Taner Karagol, Alper Karagol, & Shuguang Zhang. (2024) Structural bioinformatics studies of serotonin, dopamine and norepinephrine transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F. PLOS One (March 22, 2024). https://doi.org/10.1371/journal.pone.0300340.

Alper Karagöl, Taner Karagöl, Eva Smorodina, & Shuguang Zhang. (2024) Structural bioinformatics studies of glutamate transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, V->T, F->Y and vice versa. PLOS One (April 10, 2024). https://doi.org/10.1371/journal.pone.0289644.

Emily Pan, Fei Tao, Eva Smorodina, & Shuguang Zhang. (2024) Structural bioinformatics studies of six human ABC transporters and their AlphaFold2 predicted water-soluble QTY variants. QRB Discovery. 2024;5:e1. doi:10.1017/qrd.2024.2.

Mengke Li, Rui Qing, Fei Tao, Ping Xu, Shuguang Zhang, (2024) Inhibitory effect of truncated isoforms on GPCR dimerization predicted by combinatorial computational strategy. Computational and Structural Biotechnology Journal, 23:278-286. https://doi.org/10.1016/j.csbj.2023.12.008.