Laboratory for Computational Molecular Design

The Computational Molecular Design Group aims to simulate biomolecular interactions and to design effective molecular regulators using large-scale computer simulations. X-ray crystallography and NMR studies provide a large number of 3D structures of biomolecules, and advances in molecular detection technologies have greatly improved our understandings of intracellular molecular behaviors. To connect molecular behavior with molecular structure and to predict molecular functions, however, require large scale, atomic level molecular simulations. We are therefore focusing on molecular dynamics (MD) and quantum chemistry simulations to study this relationship in large biomolecules. Through collaboration with groups inside and outside QBiC, we are designing novel compounds for various target biomolecules by utilizing our computational techniques. Furthermore, by developing exclusive high-performance computers, we aim to achieve unprecedented long-term MD simulations.

Research Subjects

• Understanding thermodynamic and physicochemical properties of the interaction of biopolymers with their regulators and hydration water.
• Theoretical study on binding and enzymatic reactions of protein/DNA-regulator complexes.
• Designing new peptides for protein target binding.
• Development of MDGRAPE-4, a special purpose computer for MD simulations.

Publications

1. Nerukh D, Okimoto N, Suenaga A, Taiji M.:
   "Ligand Diffusion on Protein Surface Observed in Molecular Dynamics Simulation"
   J. Phys. Chem. Lett. 3.23, 3476-3479 (2012)
2. Höfinger S, Yamamoto E, Hirano Y, Zerbetto F, Narumi T, Yasuoka K, Yasui M.:
   "Structural features of aquaporin 4 supporting the formation of arrays and junctions in biomembranes"
   Biochimica et Biophysica Acta., 1818, 9, 2234-2243 (2012)
3. Yamamoto E, Akimoto T, Shimizu H, Hirano Y, Yasui M, Yasuoka K.:
   "Diffusive Nature of Xenon Anesthetic Changes Properties of a Lipid Bilayer: Molecular Dynamics Simulations"
   J. Phys. Chem. B., 116. 30, 8989-8995 (2012)
4. Otsuka T., Miyazaki T.:
   "A quantum chemistry study of Ds-Pa unnatural DNA base pair"
   Int. J. Quantum Chem., 113.4, 504-509 (2012)
5. Kondo X. H., Okimoto N., Morimoto G., Taiji M.:
   "Free-Energy Landscapes of Protein Domain Movements upon Ligand Binding"
   Journal of Physical Chemistry B, 115, 7629-6636 (2011)
6. Soda K., Shimbo Y., Seki Y., Taiji M.:
   "Structural characteristics of hydration sites in lysozyme"
   Biophys. Chem., 256, 31-42 (2011)
7. Seki Y., Shimbo Y., Nonaka T. Soda K.:
   "A New Efficient Method for Generating Conformations of Unfolded Proteins with Diverse Main-Chain Dihedral-Angle Distributions"
   J. Chem. Theory and Comput., 7, 2126-2136 (2011)
8. Harada M., Murakami H., Okawa A., Okimoto N., Hiraoka S., Nakahara T., Akasaka R., Shiraishi Y., Futatsugi N., Mizutani-Koseki Y., Kuroiwa A., Shirouzu M., Yokoyama S., Taiji M., Iseki S., Ornitz M. D., Koseki H.:
   "FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion"
   Nature Genetics, 41:3, 289-298 (2009)
9. Narumi T., Ohno Y., Okimoto N., Koishi T., Suenaga A. Futatsugi N., Yanai R., Himeno R., Fujikawa S., Taiji M., Ikei M.:
   "A 55 TFLOPS Simulation of Amyloid-forming Peptides from Yeast Prion Sup35 with the Special-purpose Computer System MDGRAPE-3"
   in Proceedings of the SC06 (2006)
10. Taiji M., Narumi T., Ohno Y., Futatsugi N., Suenaga A., Takada N., Konagaya A.:
    "Protein explorer: A petaflops special-purpose computer system for molecular dynamics simulations"
    in Proceedings of the SC2003 (2003)

Organization