Ustc researchers establish new method for protein design from scratch

2022-06-09 0 By

A team led by Professor Liu Haiyan and Associate Professor Chen Quan of the University of Science and Technology of China has pioneered a new approach to ab initio protein design based on data-driven principles, realizing the original innovation of key technologies in the frontier science and technology of protein design.It lays a solid foundation for the design of functional proteins such as industrial enzymes, biological materials and biomedical proteins.The results were published in the world’s leading journal Nature on February 10.Protein is the foundation of life and the main executor of life function. Its structure and function are determined by amino acid sequence.At present, proteins that can form stable three-dimensional structures are almost all natural proteins, whose amino acid sequences are formed by long-term natural evolution.When the structure and function of natural proteins cannot meet the needs of industrial or medical applications, it is necessary to design the structure of specific functional proteins.In recent years, the representative work of ab initio protein design in the world mainly uses natural structural fragments as building blocks to assemble artificial structures.However, this method has some disadvantages, such as single design result and too sensitive to the details of the main chain structure, which significantly limits the diversity and variability of the design main chain structure.The relevant team of USTC has been engaged in basic research and applied basic research in the direction of computational structural biology for a long time.Academician Shi Yunyu is a pioneer in this field in China.Professor Liu Haiyan and Associate Professor Quan Chen have been developing data-driven protein design methods for more than ten years.The team first established the ABACUS model for designing amino acid sequences with a given backbone structure, and then developed a SCUBA model that can design entirely new backbone structures from the ground up while the amino acid sequence is pending.Theoretical calculations and experiments show that using SCUBA to design main chain structures can overcome the limitation that only natural fragments can be splice to produce new main chain structures, thus significantly expanding the structural diversity of proteins designed from the ground up, and even designing novel structures that are different from those of known natural proteins.The SCUBA model +ABACUS model is the only fully experimental approach to protein design beyond the existing representative work, complemented by the complete tool chain for the design of artificial proteins with novel structures and sequences.In the paper, the team reports on the high-resolution crystal structures of nine de novo protein molecules, five of which have novel structures different from those of known natural proteins.