Current protein engineering methods are highly reliable, allowing the design of proteins with enhanced activity and stability. A protein’s activity or intended function involves, for example, facilitating, modifying, or directly enabling a specific chemical reaction. Stability ensures proteins maintain a consistent form; however, it is also one of the main limiting factors for their use in biomedicine.
Most of the available methods for designing proteins utilize static protein structures. Still, biomolecules, including proteins, are dynamic rather than static, and thus their dynamic properties must be considered. Protein dynamics involve, for instance, changes in their shape. Therefore, it is crucial to expand the portfolio of methods used for designing and producing proteins to include methods for engineering protein dynamics.
Consequently, researchers from the RECETOX Loschmidt laboratories at Masaryk University’s Faculty of Science and the International Center for Clinical Research ICRC-FNUSA have developed such a method in collaboration with the Masaryk Memorial Cancer Institute, Cambridge University, and Greifswald University.
The output of the six-year research project is a new platform combining experimental and computational approaches for the rational design of protein dynamics. Rational design involves systematic and iterative protein development, searching for a particular protein’s optimal structure and function. The developed platform opens entirely new possibilities for designing protein molecules with unique properties.
The platform was subsequently used for developing the luciferase protein, one of the most widely used diagnostic systems in molecular and cell biology. Luciferase accelerates the chemical reaction used by certain living organisms to emit light. This phenomenon, called bioluminescence, is produced by a chemical reaction taking place in a living organism, in which excess energy is released in the form of light.
In biomedicine, bioluminescence is used, for example, for diagnosing and studying cancer growth. Nonetheless, luciferase has several features that limit its use. For example, the light is emitted in short flashes, whereas continuous, uninterrupted light is more suitable for many practical applications.
Thanks to the newly developed method, researchers were able to modify the luciferase protein, thereby changing its light-emitting properties from flashing (for several seconds) to continuously emitting a stable light (for several minutes). The modified luciferase protein provides researchers an invaluable tool for biomedical research and biotechnological applications. The method described above was recently published in the journal Nature Communications.
The method described above was featured on the Editor’s Highlights Nature Communications page, which showcases the 50 best papers recently published in an area.