We will establish a research field of the generative design that enables conversion and creation of protein molecular functions. Protein molecules, which are responsible for biological functions, have been continuously changing in the evolution to adapt to the environment, resulting in diverse and highly capable molecular functions.
However, the protein molecules that have emerged in this evolution are only a small fraction of the theoretically possible set of protein molecules, and design studies of artificial proteins that do not exist in nature suggest that there are an enormous number of protein molecules that have not yet appeared in the evolution. Protein molecules therefore have immense potential for modification of their molecular functions and generation of new ones.
We therefore aim at establishing guiding principles to design protein molecules with new functions in a “generative” manner. We will develop a methodology for designing functional protein molecules based on the requirement definitions for the novel function, rather than a heuristic search. For that purpose, we will integrate theoretical methods based on computational chemistry and data science, spatiotemporal measurements, and protein molecule development technologies.
When a protein performs a remarkable molecular function, it often generates a “functional state” that appears instantaneously and activates the function. Recently, it has become possible to accurately predict and analyze the functional states using advanced computational methods. In addition, time-resolved x-ray crystallography has made it possible to directly observe experimentally the movement of molecules in three-dimensional space in functional states. By making full use of the state-of-art computational and experimental techniques, we identify functional features that determine protein molecular functions, and theoretically design protein mutants of modified functions by directly analyzing the functional features. Then, by forming a feedback loop with experimental studies on the development of novel functional proteins that contribute to medicine, drug discovery, and creation of new substances, we will establish the theory of the generative design of protein functions.
