Structure-based Molecular Design Team

We plan to develop methods for designing novel small molecules, nucleic acids, and proteins, in order to help to accelerate drug development and the elucidation of living systems, and also develop an FBDD (Fragment based Drug Discovery) method for targeting biomolecules currently difficult to make susceptible of binding to small molecules.

Research Fields

Chemistry / Pharmacology & Toxicology / Computer Science

Research Subjects

• Development of new technologies for in silico screening and the applications
• Construction of FBDD platform for difficult drug discovery targets
• Development of simulation/design technologies for unnatural nucleic acid/protein

Publications

1. *Saito, Y.; Yuki, H.; Kuratani, M.; Hashizume, Y.;Takagi, S.; Honma, T.; Tanaka, A.; Shirouzu, M.; Mikuni, J.; Handa, N.; Ogahara, I.; Sone, A.; Najima, Y.; Tomabechi, Y.; Wakiyama, M.; Uchida, N.; Tomizawa-Murasawa, M.; Kaneko, A.; Tanaka, S.; Suzuki, N.; Kajita, H.; Aoki, Y.; Ohara, O.; Shultz, L.D.; Fukami, T.; Goto, T.; Taniguchi, S.; Yokoyama, S.; Ishikawa, F.
   "A pyrrolo-pyrimidine derivative targets human primary AML stem cells in vivo."
   Science Translational Medicine, 2013, in press.
2. *Takaya, D.; Sato, T.; Yuki, H.; Sasaki, S.; Tanaka, A.; Yokoyama, S.; Honma, T.
   "Prediction of Ligand-Induced Structural Polymorphism of Receptor Interaction Sites Using Machine Learning."
   J Chem Inf Model, 2013, in press.
3. *Sato, T.; Watanabe, H.; Tsuganezawa, K.; Yuki, H.; Mikuni, J.; Yoshikawa, S.; Kukimoto-Niino, M.; Fujimoto, T.; Terazawa, Y.; Wakiyama, M.; Kojima, H.; Okabe, T.; Nagano, T.; Shirouzu, M.; Yokoyama, S.; Tanaka, A.; Honma, T.
   "Identification of novel drug-resistant EGFR mutant inhibitors by in silico screening using comprehensive assessments of protein structures."
   Bioorg Med Chem, 2012, 20(12), 3756-67.
4. *Sato, T.; Yuki, H.; Takaya, D.; Sasaki, S.; Tanaka, A.; Honma, T.
   "Application of Support Vector Machine to Three-Dimensional Shape-Based Virtual Screening Using Comprehensive Three-Dimensional Molecular Shape Overlay with Known Inhibitors."
   J Chem Inf Model, 2012, 52(4), 1015-1026.
5. *Yuki, H.; Honma, T.; Hata, M.; Hoshino, T.
   "Prediction of sites of metabolism in a substrate molecule, instanced by carbamazepine oxidation by CYP3A4."
   Bioorg Med Chem, 2011, 20(2), 775-83.
6. *Sato, T.; Honma, T.; Yokoyama, S.
   "Combining Machine Learning and Pharmacophore-based Interaction Fingerprint for in silico Screening."
   J Chem Inf Model, 2010, 50(1), 170-85.
7. *Sato, T.; Matsuo Y.; Honma, T.; Yokoyama, S.
   "In silico functional profiling of small molecules and its applications."
   J Med Chem, 2008, 51(24), 7705-16.
8. *Sakiyama Y.; Yuki, H.; Moriya, T.; Hattori, K.; Suzuki, M.; Shimada, K.; Honma, T.
   "Predicting human liver microsomal stability with machine learning techniques."
   J Mol Graph Model, 2008, 26(6), 907-915.
9. *Kawai, M.; Sakurada, I.; Morita, A.; Iwamuro, Y.; Ando, K.; Omura, H.; Sakakibara, S.; Masuda, T.; Koike, H.; Honma, T.; Hattori, K.; Takashima, T.; Mizuno, K.; Mizutani, M.; Kawamura, M.
   "Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation."
   Bioorg Med Chem Lett, 2007, 17(20), 5537-5542.
10. *Honma, T.
    "Recent advances in de novo design strategy for practical lead identification."
    Med Res Rev, 2003, 23 (5), 606-632.