Team

We integrate theoretical methods based on computational chemistry and data science, spatio-temporal measurements, and protein molecule development technologies.

Researches are conducted in two layers: the analytical layer and the generative one. In the analysis layer, functional features are identified. We then design theoretical modifications and generate new functions in the generative layer.

Area PI and A01 PI: Shigehiko Hayashi (Kyoto University)

We aim at developing a methodology for the theoretical design of protein functions. Through identification of molecular features in functionally activated states with an advanced hybrid molecular simulation, amino acid mutations that alter protein functions are predicted theoretically.

A01 Co-I: Akio Kitao (Tokyo Institute of Technology)

We investigate activation/inactivation mechanisms of protein/ligand complexes by cutting edge molecular simulation and free energy analysis such as parallel cascade selection molecular dynamics (PaCS-MD) and Markov state model (MSM).

Research Collaborators

A02 PI: Florence Tama (Nagoya University and RIKEN Center for Computational Science)

We investigate the structure, function, and dynamics of biomolecules through the development and application of integrative modeling computational tools that combine experimental data from various sources, including X-ray crystallography, cryo-EM, SAXS, and AFM, with molecular dynamics simulations.

A02 Co-I: Osamu Miyashita (RIKEN Center for Computational Science)

My research focuses on developing computational tools for experimental data analysis and structural modeling. This project specifically targets the analysis of time-resolved experimental data from X-ray free electron lasers and the interpretation of conformational ensembles derived from SAXS and cryo-EM data.

Research collaborators

A03 PI: Nobuyasu Koga (Osaka University)

The protein sequence space is enormously vast. Naturally occurring proteins represent only a tiny fraction ofthis immense sequence space. Using both computational and experimental approaches, We explore fundamental principles and methodologies for designing protein molecules. Current focus is on developing methods to provide functions to de novo designed protein structures.

A03 Co-I: Rie Tatsumi (Osaka University)

Research collaborators

B01 PI: Eriko Nango (Tohoku University)

I am working on the development of technology for time-resolved serial crystallography of proteins using an X-ray free electron laser. I will perform time-resolved measurements at SACLA to apply precise dynamic structures to protein design.

B01 Co-I: Masahiro Fukuda (University of Tokyo)

My research interest is to visualize the molecular dynamics of various types of membrane proteins in atomic resolution. I believe that time-resolved (TR) cryo-EM analysis will open the door for the next-generation molecular movie field in combination with TR-SFX method.

Research Collaborators

B02 PI: Minoru Kubo (University of Hyogo)

My area of expertise is spectroscopy. We will use infrared (IR), Raman, circular dichroism (CD), and small-angle X-ray scattering (SAXS) techniques to analyze a wide range of protein motions, from the microscopic dynamics in an active site to the conformational ensemble change in an intrinsically-disordered region of proteins.

B02 Co-I: Misao Mizuno (Kyoto University)

We observe functionally important structural changes in proteins using time-resolved resonance Raman spectroscopy under physiological conditions. Comprehensive understanding of our observations with results obtained by other experimental measurements as well as simulations will help to elucidate protein mechanisms, especially for photoreactive proteins.

Research Collaborators

B03 PI: Tomohiro Nishizawa (Yokohama City University)

B03 Co-I: Yongchan Lee (Yokohama City University)

My research focuses on studying the structural dynamics of membrane transporters using cryo-EM. Many of them are known to form functional complexes inside the cells – these will be the target for rational design and modification in this research area.

Research Collaborators

C01 PI: Shigeki Kiyonaka (Nagoya University)

My research focus is the development of artificial receptors that can be selectively activated by designer ligands, which is known as chemogentics. Our goal is to generatively design the artificial receptors in collaboration with the other group members mainly focusing on structural and theoretical studies. 

C01 Co-I: Hidetsugu Asada (Kyoto University)

My research interests lie in the structural analysis of membrane proteins, with a particular focus on G-protein coupled receptors (GPCRs). The objective is to identify and support the development of suitable compounds for drug discovery. The goal of this research area is to generatively design the effective GPCRs based on their structure.

Research Collaborators

C02 PI: Tsuyoshi Hirota (Nagoya University)

We discovered unique compounds against the circadian clock protein CRY that is related to various diseases. By combining these compounds with dynamic structural analysis, molecular simulation, and generative design, we will elucidate the structural polymorphism of CRY and enable its control for circadian drug discovery.

C02 Co-I: Kazuma Amaike (Nagoya University)

We focus on the design and synthesis of bioactive molecules. In this project, we will investigate circadian clock modulators with high bioactivity and also design and synthesize molecules to elucidate their molecular mechanisms.

Research Collaborators

C03 PI: Robert E. Campbell (University of Tokyo)

My research involves the use of protein engineering, directed evolution, and chemical biology for the development of genetically encoded tools for fluorescence imaging and illumination-dependent control of cells and tissues. Our current focus is on developing far-red and near-infrared fluorescent biosensors for imaging of neural activity and metabolism.

C03 Co-I: Takuya Terai (University of Tokyo)

My research interest is in the development of functional molecular tools using the synergistic power of organic chemistry and molecular biology. In particular, we aim to develop near-infrared chemigenetic fluorescent sensors based on protein design.

Research Collaborators

C04 PI: Keiichi Inoue (University of Tokyo)

Microbial rhodopsins are photoreceptive membrane proteins and key optogenetic tools that transport a variety of ions using light energy. Our research aims to create novel functional rhodopsins through a synergy of experimental and computational approaches.

C04 Co-I: Kazuhiro J. Fujimoto (Nagoya University)

My research interest lies in the excited states of molecules in chemical and biological systems. At our laboratory, we are trying to theoretically and computationally elucidate the molecular mechanisms underlying electron transfer, excitation energy transfer, and intersystem crossing.

Research Collaborators

C05 PI: Shinya Fushinobu (University of Tokyo)

We have been studying various carbohydrate-active enzymes (CAZymes) and related enzymes, with a focus on those beneficial to industry and human health. Utilizing molecular movies and other advanced methodologies, we aim to unravel the complex reaction mechanisms of these valuable enzymes.

C05 Co-I: Akihiro Ishiwata (RIKEN)

My research focuses on the structure- and mechanism-based molecular design and synthesis of probesfor molecular movie analysis of dynamic catalysis of useful enzymes. Synthetic probes could be prepared especially for carbohydrate-acting enzymes, corresponding to each unique mechanism.

Research Collaborators