11/22(水)17:00 -  Qian-Yuan Tang氏 (Dept. of Physics, Hongkong Baptist Univ.)

" Exploring protein evolution and dynamics through the lens of AlphaFold "

AlphaFold, a groundbreaking AI tool developed by DeepMind, has significantly advanced the field of protein structure prediction and ushered in a new era of life science research. The transformative potential of AlphaFold's high predictive accuracy has not only broadened the horizons of life science research, but has also provided profound insights into the evolution and dynamics of proteins. In this seminar, I will first provide a brief overview of the underlying mechanisms of AlphaFold 2, followed by an exploration of our recent breakthroughs in the field of protein evolution and dynamics through the application of statistical physics methods, all rooted in the AlphaFold database. (i) On protein evolution, our research involves a comparative analysis of proteins from more than 40 model organisms. This has revealed remarkable statistical trends in protein evolution (Mol. Biol. Evol. 39(10), msac197, 2022). In organisms of higher complexity, we observed that constituent proteins exhibit larger radii of gyration, increased flexibility, and a greater degree of spatial and sequence segregation between hydrophobic and hydrophilic residues. In addition, our statistical physics analysis has revealed a significant statistical correlation between increased organismal complexity and increased functional specialisation of constituent proteins. These findings provide a crucial link between molecular and organismal evolution, enriching our understanding of the origins and evolution of life. (ii) On protein dynamics, we will delve into the protein structure prediction uncertainty and its correlation with protein dynamics. Our results further confirm the concept of dynamics-evolution correspondence in protein structures (Phys. Rev. Lett. 127, 098103, 2021). This discovery suggests an evolutionary mechanism by which proteins acquire both dynamical flexibility and evolutionary structural variability.