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De novo Design of a Protein Biosensor Platform Through Computational Protein Design Approach

The organic materials, called proteins,are evolved for billion years. However, the number of the natural proteins is few. The story is different, if artificial proteins can be synthesized by humans. The possible number of protein combinations consisting 100 amino acid sequences with 20 different types of amino acids is 20100, which is an astronomical number. Therefore, scientists are endeavoring to synthesize artificial proteins.
In line with this, Professor Oh’s group conducted a joint study with the Institute for Protein Design at University of Washington, US, and developed a platform that can be used to manufacture high-sensitivity protein biosensors. Biosensors are used for a number of purposes, including diagnosis of disease, tracking disease progress, and detection of pathogenic microorganisms. Conventionally, proteins sensors were developed by using natural proteins directly or by slightly modifying them. However, Professor Oh’s group manufactured a high-sensitivity protein sensor by using artificial proteins that do not exist in the nature.

|Creating Protein-Sensor Platform with Proteins That Do Not Exist in Nature|

Creating a protein biosensor platform
“One class of the artificial proteins is scaffold protein, which has only the structure without a function. The significance of our study is that we have granted a function to a scaffold protein, and the sensitivity of the sensing function was much higher than that of the existing protein sensors. Furthermore, we performed recombination of a light-emitting protein (luciferase) from deep sea shrimp to make the sensing system highly sensitive.”
Another meaningful point is that the accomplishment is oriented to the development of not one type of protein sensor but a platform that can be applied more extensively in the future. This suggests that what they manufactured was not a sensor that reacts to a single target material, but a platform that can be used to prepare different sensors by changing the target binding protein attached to the platform. Professor Oh compares this to LEGO.
“Like the LEGO blocks that can be used to create different shapes, our LEGO blocks, composed of the platform that we created, can be used to make different biosensors by combining it with a protein that binds to a target of interest. Actually, using this platform, we were able to create eight different, high-sensitivity protein biosensors that responds to eight different targets, including Type B hepatitis virus and coronavirus. The sensitivity of our sensor was much better than that of existing ones.”

Creation of artificial protein functions and presentation of possibilities for commercialization
The underlying mechanism of the protein biosensor developed by the research group is not found in the nature. This means that the technology went beyond the imitation of the nature, even to the point of creating proteins and their functions that do not exist in the nature. Professor Oh said that people described him as strongly tenacious, when he gave up his sabbatical year for the study. He has a positive view about the technology that it can be commercialized through on-site application such as clinical studies. The technology is also attractive as it can be easily commercialized in a start-up scale, unlike the medical devices that have to step over many huddles to be commercialized.
With the support from LG Yonam Foundation, the Professor Oh’s group conducted the study by visiting Professor David Baker’s lab at University of Washington, US, for one year. The results of the study were published in Nature, a globally acclaimed international journal of sciences (published on January 27, 2021).

Prof.Byung-ha Oh
2021 Annual Report

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