Theme2 Simulation applicable to drug design

Theme2

Simulation applicable to drug design

-Simulation to predict activities of innovative drugs-

Group Leader:

Hideaki Fujitani
(Research Center for Advanced Science and Technology, The University of Tokyo)

Simulation of protein-compound interaction

Interaction between antigen and antibody

Summary

Since many drugs target proteins, we have to find a compound that interacts strongly with the intravital target protein (ligand) to discover a more effective drug. We aim at rapid and efficient development of low molecular weight drugs in the following manner. By use of molecular dynamics calculations using the K computer, we run a simulation of a system including a target protein and a drug candidate compound, investigate protein-compound interaction, and design a new compound which acts only on the target protein.

Approach during the Past Five Years and its Achievements

Publications

1. Hideaki Fujitani, Keiko Shinoda, Takefumi Yamashita, and Tatsuhiko Kodama:
“High performance computing for drug development on K computer“
J. Phys.: Conf. Ser. 454 012018 (2013)

2. Takefumi Yamashita, Akihiko Ueda, Takashi Mitsui, Atsushi omonaga, Shunji Matsumoto, Tatsuhiko Kodama, Hideaki Fujitani:
“Molecular Dynamics Simulation-Based Evaluation of the Binding Free Energies of Computationally Designed Drug Candidates: Importance of the Dynamical Effects”
Chemical and Pharmaceutical Bulletin vol.62 pp. 661-667 (2014)

3. Takefumi Yamashita:
“Improvement in Empirical Potential Functions for Increasing the Utility of Molecular Dynamics Simulations”
JPS Conf. Proc. 5, 010003 (2015)

4. Takefumi Yamashita, Akihiko Ueda, Takashi Mitsui, Atsushi Tomonaga, Shunji Matsumoto, Tatsuhiko Kodama, Hideaki Fujitani:
“The Feasibility of an Efficient Drug Design Method with High-Performance Computers“
Chemical and Pharmaceutical Bulletin,  vol. 63, pp. 147–155 (2015)

5. Nakayama, Mizohata, Yamashita et al.,:
“Structural features of interfacial tyrosine residue in ROBO1 fibronectin domain-antibody complex: Crystallographic, thermodynamic, and molecular dynamic analyses“
Protein Sciecne vol 24(3) pp 328-340 (2015)

Group organization

As of April 1, 2015

Other Themes

Theme1 Simulations of biomolecules under cellular environments

By developing molecular-level simulation methods and carrying out research on potential applications, we are working to elucidate biological phenomena at the cellular level, and by doing to make possible new therapies and develop new drugs.

Theme3 Hierarchical integrated simulation for predictive medicine

Simulations have been developed for different organ systems, such as the circulation, musculature, skeleton, brain, and nervous system. By integrating them, we will be able to gain an understanding of complex conditions such as heart disease and movement disorders, and to develop optimal personalized medicine to treat these illnesses.

Theme4 Large-scale analysis of life data

Cancer and metabolic syndrome are of the biggest interest in health for the people.

Our high-speed and high-performance analysis of large-scale life data, such as genomic information, contributes to the progress of personalized medicine to tackle cancer and other diseases.