As we all know, proteins are the material basis of all living systems, intimately involved in every physiological process from triggering an immune response to signal processing in the brain.
Protein design relies on the precise simulation of the macromolecular model. Based on the relationship between protein structure and function, the technology means of various disciplines are comprehensively applied to obtain new proteins with better performance than natural proteins. Different from modifying natural proteins as seen in conventional protein design, de novo protein design seeks to construct protein molecules from scratch, with specific structure and function. Therefore it is regarded as a difficult problem.
Zibo Chen embarked on a quest to engineer modular interactions into designed proteins under the supervision of leading researchers in protein design, Dr. David Baker and Dr. Frank DiMaio, during his Ph.D. study at the University of Washington.
By precisely designing the buried hydrogen bond network of proteins to achieve binding specificity between proteins (similar to the binding properties of base-pairing of A-T/G-C in DNA), he succeeded in designing and verifying highly specific protein homo- and hetero-dimers from scratch, both of which are not found in nature. This is the first time in the field anyone has engineered such novel interaction modalities (the protein equivalent of DNA base pairing) into proteins.
Additionally, Zibo Chen successfully self-assembled 2D materials with designed protein building blocks during his PhD research and demonstrated how a single protein building block could be designed into two different array geometries by modularly optimizing the sequences at the binding interface. This work opens the door to the creation of programmable protein-based materials.
We believe that his research will provide a programmable, customizable toolbox in the field of synthetic biology, especially in the design of cellular pathways from the ground up, and will play a huge role in human health and new materials.