Biological Function and Information Group

Chief

shigeta

Yasuteru Sigeta, Professor

Dr. Yasuteru Shigeta graduated from Department of Chemistry, Osaka University in 2000. Following his graduation, he initially served as a postdoctoral fellow of Japan Society for the Promotion Science working at the University of Tokyo. He served as an assistant professor in the University of Tokyo (2004), a Lecturer in University of Tsukuba (2007), an associate professor in University of Hyogo(2008), and an associate professor in Osaka University (2010). Since 2014, he joined the Center for Computational Sciences (CCS) in the University of Tsukuba as a full professor.

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About our group

What is the key difference between living organisms and non-living matter? In simpler words: what is life? The answer is still unknown, despite intensive efforts by many scientists over the years. The purpose of our research division is to clarify such fundamental questions in life sciences. To this aim, we have approached these research topics starting from the investigation of physical, chemical, and biological mechanisms of functions and structures of biological macromolecules, by using high-level computational methodologies.

Since 3D structures of proteins, RNA, DNA, etc., are, in general, huge and complicated, we have developed hybrid quantum mechanics (QM) / molecular mechanics (MM) high-performance and high-accuracy computational techniques coupled to molecular dynamics (MD) simulation (this is referred to as QM/MM MD calculations), to shed some light into the electronic- and 3D-structural dynamics of biological molecules.

Furthermore, to elucidate functional mechanisms of biological systems such as transcriptional regulation network systems, we have developed an identification system of transcriptional factor binding motifs (TFBMs) on genome DNA sequences, which is currently the best program to find TFBMs. In this system, statistical techniques and information sciences are exploited to build the identification algorithm. Based on such informatical techniques, we aim to identify experimentally-unknown TFBMs as well as known ones, and to reconstruct transcriptional regulation network systems in living organisms.

Research topics

  1. Elucidation of the detailed mechanisms of high-efficiency enzymatic reactions and proton/electron transfer based on electronic/3D structures of biological macromolecules, by using our hybrid QM/MM MD calculation system.
  2. Elucidation of the detailed molecular mechanisms at the system-level: Development and application of high-performance and high-accuracy algorithms to find functional signals on genome DNA sequences and to reconstruct regulation network systems of biological functions involving iPS cells and critical diseases such as cancer.


Fig.1 The dynamical reaction mechanism of hybrid ribozyme/protein catalyst revealed by hybrid QM/MM MD simulations.

Recent Significant Research Achievements

Our computational analyses of dynamical reaction mechanisms operated by biological macromolecules have actually led to the detailed understandings of functional roles of structural elements in proteins and RNA/DNA molecules [1, 2]. As one of the results, we have discovered a novel enzyme category, i.e., the hybrid ribozyme/protein catalyst, which is widely spread in various biological systems [2]. This is another (the third) type of enzymes added to the protein and RNA enzymes.

  1. Hagiwara, Y., Matsumura, H., and Tateno, M., J. Am. Chem. Soc., 131 (2009), 16697-705.
  2. Hagiwara, Y., Field, M., Nureki, O., and Tateno, M., J. Am. Chem. Soc., 132 (2010), 2751-58.