Mechanically Interlocked Proteins

 

Mechanically Interlocked Proteins

 

Date: 23^rd March, 2026 (Monday)

Time: 5 - 5:50 pm (HKT)

 

Venue: Lecture Theatre T5, Meng Wah Complex

 

 

College of Chemistry and Molecular Engineering

Peking University

 

Wen-Bin Zhang received his BS from Peking University in 2004 and his PhD in Polymer Science from the University of Akron in 2010. He continued there as a postdoc for one year, before moving to Caltech for a second postdoc. He started his independent career at Peking University in 2013 and was promoted to a tenured associate professor in 2019 and to a full professor with tenure in 2020. His goal is to integrate the design principles and building blocks of both synthetic and biological polymers for the development of precision macromolecules with unique functions for health-related applications. He has been an editor of Bioorganic Chemistry since 2021 and the committee member for the Division of Supramolecular Chemistry of Chinese Chemical Society and for the Division of Autoimmunity, Chinese Society for Immunology. To date, he has published over 180 peer-reviewed papers in Science, PNAS, JACS, ACIE, etc. and has received many awards including the “Distinguished Lectureship Award” from the Chemical Society of Japan in 2017, the Distinguished Young Scholars Award from the National Natural Science Foundation of China in 2019, the Bayer Investigator Award in 2021, and the Lectureship Award for Innovative Young Supramolecular Chemists, Chinese Chemical Society, in 2023.

 

The chain structure design, precise synthesis and structure-activity relationship of topological polymers have always been a major challenge in polymer synthesis. As a class of biomacromolecules, proteins provide an ideal platform for studying topological macromolecules. In this talk, I will discuss artificial intelligence assisted design of topological proteins. By splitting the protein domain at the loop region and rewiring the resulting fragments, proteins with target unconventional topology will be automatically designed via a program called TopoDesign. We show that this is broadly applicable to a variety of enzymes, cytokines, and other functional proteins with high success rate. It leads to a database of topological fingerprints for establishing the relationship between the fold-type and its preferred topology. These studies will provide guidelines and typical cases for the design and precision synthesis of topological macromolecules, create new categories and research objects for protein science, and lay a solid foundation for the practical application of topological proteins.

 

(1) Qu, Z.; Xu, L.; Jiang, F.; Liu, Y.; Zhang, W.-B.* Folds from Fold: Exploring Topological Isoforms of a Single Domain Protein. Proc. Natl. Acad. Sci. USA 2024, 121, e2407355121.

(2) Liu, Y.; Tian, X.; Zhang, F.; Zhang, W.-B.* Probing the Topological Effects on Stability Enhancement and Therapeutic Performance of Protein Bioconjugates: Tadpole, Macrocycle versus Figure-of-Eight. Adv. Healthcare Mater. 2024, 13, 2400466.

(3) Qu, Z.; Fang, J.; Wang, Y.-X.; Sun, Y.; Liu, Y.; Wu, W.-H.; Zhang, W.-B.* A single-domain green fluorescent protein catenane. Nat. Commun. 2023, 14, 3480.

(4) Fang, J.; Li, T.; Lee, J.; Im, D.; Xu, L.; Liu, Y.; Seo, J.; Zhang, W.-B.* A single-domain protein catenane of dihydrofolate reductase. Natl. Sci. Rev. 2023, 10, nwad304.

 

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