To the text

HOME > Group Introduction > Biological Data Science Research Group

Biological Data Science Research Group

Biological Data Science Group Research Group Overview

One of the defining features of our research group is the seamless integration of wet and dry research. We not only develop innovative in silico technologies to support drug discovery, but also drive Bio × AI–integrated research by harnessing the synergy between experimental and computational approaches. In this framework, modification-omics data and therapeutic modalities obtained through proprietary omics measurement and cell-control technologies are further advanced using theoretical modeling and AI. Our mission is to accelerate breakthroughs in drug discovery, diagnostics, and treatment technologies. Furthermore, we are fostering the next generation of researchers who excel in both wet and dry research domains.

Biological Data Science Research Group Overview

Research Project

project 1:Advancing Drug Discovery for Undruggable Targets: Technology Development and Applications
Researcher:KOSEKI Jun, NAKAMURA Yuki, MOTONO Chie, IMAI Kenichiro

In recent years, even when potential drug targets are identified, many of them remain undruggable, leading to a depletion of viable drug targets and posing a significant societal challenge. To address this issue, we have developed a method called CrypToth, which enables the identification of previously undiscovered molecular binding sites (cryptic sites) in disease-related proteins that are considered undruggable. Building on the cryptic sites identified by CrypToth, we leverage artificial intelligence (AI) technologies to support the development of targeted protein degraders and allosteric modulators. Through these efforts, we aim to establish a foundational technology that enables access to previously undruggable targets in drug discovery.

Biological Data Science Group Research Group2

Project 2:Development of Novel Diagnostics and Therapeutics through Multimodal Data Analysis Leveraging Omics Modifications
Researcher: KONNO Masamitsu, IMAI Kenichiro

RNA modifications are known to be altered across a wide range of diseases. However, due to the immaturity of current measurement technologies, their application to diagnosis and therapy has not yet been realized. To address this challenge, we are developing novel technologies for the precise measurement of RNA modifications. Furthermore, by integrating these data with other omics datasets and diagnostic imaging through AI-driven multimodal analysis, we aim to advance early diagnostic technologies and develop new therapeutic strategies for cancer and other diseases.

Biological Data Science Group Research Group3

Project 3: Development of herpesvirus vectors as a drug modality
Researcher:MAEDA Fumio, KOSEKI Jun, IMAI Kenichiro)

The herpes simplex virus (HSV) Amplicon vector eliminates the viral genome from the viral particle and packages a plasmid instead, and is a viral vector characterized by (1) the limited cytotoxicity, (2) the large transgene capacity of up to 150 kb, and (3) the broad host range of vector transduction. We are currently developing methods for efficient production of HSV vectors, retargeting them, and utilizing HSV vectors as a gene therapy drug.

Biological Data Science Group Research Group4

Project 4:Search for undiscovered protein functional sites based on the spatial distribution of disease-associated missense variants
Researcher:MOTONO Chie, KAGIWADA Harumi, KOSEKI Jun, IMAI Kenichiro

Effective utilization of large number of disease-associated variants revealed through sequencing projects is one of the major challenges in medical and pharmaceutical field. Disease-associated missense variants (DAMVs) tend to gather around functional sites such as ligand binding sites and PPI interfaces. In this study, we comprehensively defined 3D variant clusters by clustering of the spatially-distributed DAMVs on human protein structures utilizing AlphaFold2 predicted structures. The 3D variant clusters not related to known functional sites would indicate undiscovered functional sites such as cryptic sites or allosteric sites. We are developing method for prediction of novel functional sites leading to novel drug targets based on the 3D variant clusters by integrating mixed sequence analysis, machine learning and solvent molecular dynamics simulation.

Biological Data Science Group Research Group5

Project 5:Protein network dynamics analysis
Researcher: KAGIWADA Harumi, IMAI Kenichiro

Protein phosphorylation is one of the representative mechanisms of post-translational modification which regulates enzyme activities and transduces signaling pathways. Here we developed a novel and convenient system for a series of phosphorylation analyses. By our system, the active pathways can be visualized on the pathway map to facilitate biological interpretation depending on the different cases such as disease-control and drug treatment. Pathway analysis results of drug response using this system have been collected and published as Phosprof database.

Biological Data Science Group Research Group6

Member

photo position & name field of expertise and other info
Imai's photo Research Group Leader/Attached to Research Group IMAI Kenichiro
  • Development of support technologies for drug discovery, treatment, diagnosis based on data science and bioinformatics
  • Development of in silico drug discovery support technology for undruggable targets
  • Development of next-generation viral vectors through in silico molecular design
Konno's photo Chief Senior Researcher KONNO Masamitsu
  • Development of new diagnostic and therapeutic methods for diseases using omics data
  • Development of novel technologies to analyze trans-omics information based on the epitranscriptome
  • Elucidation of the functions of modifying factors that regulate the biological system
Koseki's photo Senior Researcher KOSEKI Jun
  • Development of drug discovery support technology based on theoretical structural analysis
  • Establishment of a molecular function analysis method using topological data analysis
  • Design of molecules with specific functions using theoretical science and machine learning methods
Kakiwada's photo Senior researcher KAGIWADA Harumi
  • Phosphorylation profile measurement using protein array
  • Pathway activity analysis based on phosphorylation profile
  • Phosprof: pathway analysis database of drug response based on phosphorylation profile
Maeda's photo Senior Researcher MAEDA Fumio
  • Development of Re-targeted HSV vectors
  • Development of intercellular transport system using HSV vectors
  • Development of intracellular information acquisition technology using HSV vectors
NAKAMURA's photo Researcher NAKAMURA Yuki
  • Computational discovery of druggable target sites and drug design
Motono's photo Attached to Research Institute/Career Researcher MOTONO Chie
  • Elucidation of disease mechanisms and support for drug discovery by molecular dynamics simulations
  • Bio-manufacturing by molecular dynamics simulations and machine learning
  • Search for novel drug targets based on the spatial distribution of disease-associated missense variants

Results

  • Bekker, GJ; Fukunishi, Y; Higo, J; Kamiya, N.
    Assessment of RNA Force Fields for Dynamic Docking of Small Molecules Using Multicanonical MD Simulations.
    JOURNAL OF CHEMICAL THEORY AND COMPUTATION. 2025 Oct 22. doi:10.1021/acs.jctc.5c01114
  • Ojima-Kato, T; Yokoyama, G; Nakano, H; Hamada, M; Motono, C.
    Screening and machine learning-based prediction of translation-enhancing peptides that reduce ribosomal stalling in Escherichia coli.
    RSC CHEM BIOL. 2025 Oct 22. doi:10.1039/d5cb00199d
  • Hara, T; Meng, S; Motooka, D; Arao, Y; Saito, Yk Rennie, S; Uchida, S; Ofusa, K; Arai, T; Konno, M; Satoh, T; Ishii, H.
    Deficiencies in methionine, tryptophan, and niacin remodels intestinal transcriptome and gut microbiota in female mice.
    SCI REP. 2025 Oct 16;15(1):36155. doi:10.1038/s41598-025-18046-2
  • Lintuluoto, M; Horioka, Y; Fujiwara, M; Abe, M; Fukunishi, Y; Tamura, H; Lintuluoto, JM.
    Investigation on the Substrate Specificity of Serine Protease Neuropsin by Molecular Dynamics Simulation and Marmoset Gene Atlas (MGA.
    ACS OMEG. 2025 JUN 2. doi:10.1021/acsomega.5c00843
  • Motono, C; Yanagisawa, K; Koseki, J; Imai, K.
    CrypTothML: An Integrated Mixed-Solvent Molecular Dynamics Simulation and Machine Learning Approach for Cryptic Site Prediction.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2025 May 14;26(10):4710. doi:10.3390/ijms26104710
  • Koseki, J; Motono, C; Yanagisawa, K; Kudo, G; Yoshino, R; Hirokawa, T; Imai, K.
    CrypToth: Cryptic Pocket Detection through Mixed-Solvent Molecular Dynamics Simulations-Based Topological Data Analysis.
    JOURNAL OF CHEMICAL INFORMATION AND MODELING. 2025 May 22. doi:10.1021/acs.jcim.4c02111
  • Nobe, M; Maruzuru, Y; Takeshima, K; Maeda, F; Kusano, H; Yoshimura, R; Nishiyama, T; Park, H; Kozaki, Y; Iwami, S; Koyanagi, N; Kato, A; Natsume, T; Adachi, S; Kawaguchi, Y.
    Direct relationship between protein expression and progeny yield of herpes simplex virus 1.
    MBIO. 2025 May 5:e0028025. doi:10.1128/mbio.00280-25
  • Ohkawa, M; Ohshiro, T; Koseki, J; Kon, S; Ozeki, Y; Taniguchi, M; Shimamura, T; Konno, M.
    New RNA modifications induce malignancy for pancreatic cancer.
    CANCER SCIENCE. 2025 Mar. doi: 10.1111/cas.16114
  • Yamagishi, A; Tokuoka, R; Imai, K; Mizusawa, M; Susaki, M; Uchida, K; Kijima, ST; Nagasaki, A; Takeshita, D; Yoshikawa, C; Uyeda, TQP; Nakamura, C.
    Nestin Forms a Flexible Cytoskeleton by Means of a Huge Tail Domain That Is Reversibly Stretched and Contracted by Weak Forces.
    CELLS. 2025 Jan 17;14(2):138. doi:10.3390/cells14020138
  • Sato, T; Abe, K; Koseki, J; Seto, M; Yokoyama, J; Akashi, T; Terada, M; Kadowaki, K; Yoshida, S; Yamashiki, YA; Shimamura, T.
    Survivability and life support in sealed mini-ecosystems with simulated planetary soils.
    SCI REP. 2024 Nov 1;14(1):26322. doi: 10.1038/s41598-024-75328-x
  • Yoshinori, F; Imai, K; Horton, P.
    Prediction of mitochondrial targeting signals and their cleavage sites.
    METHODS ENZYMOL. 2024 Sep 11. doi: 10.1016/bs.mie.2024.07.026
  • Fujii, Y; Kamata, K; Gerdol, M; Hasan, I; Rajia, S; Kawsar, SMA; Padma, S; Chatterjee, BP; Ohkawa, M; Ishiwata, R; Yoshimoto, S; Yamada, M; Matsuzaki, N; Yamamoto, K; Niimi, Y; Miyanishi, N; Konno, M; Pallavicini, A; Kawasaki, T; Ogawa, Y; Ozeki, Y; Fujita, H.
    Multifunctional Cell Regulation Activities of the Mussel Lectin SeviL: Induction of Macrophage Polarization toward the M1 Functional Phenotype.
    MARINE DRUGS. 2024 Jun 11;22(6):269. doi: 10.3390/md22060269
  • Watanabe, A; Koyano, F; Imai, K; Hizukuri, Y; Ogiwara, S; Ito, T; Miyamoto, J; Shibuya, C; Kimura, M; Toriumi, K; Motono, C; Arai, M; Tanaka, K; Akiyama, Y; Yamano, K; Matsuda, N.
    The origin of esterase activity of Parkinsons disease causative factor DJ-1 implied by evolutionary trace analysis of its prokaryotic homolog HchA.
    J BIOL CHEM. 2024 Jun 13:107476. doi: 10.1016/j.jbc.2024.107476
  • Higo, J; Bekker, GJ; Kamiya, N; Fukuda, I; Fukunishi, Y;.
    Binding free-energy landscapes of small molecule binder and non-binder to FMN riboswitch: All-atom molecular dynamics.
    BIOPHYS PHYSICOBIOL. 2023 Dec 13;20(4):e200047. doi: 10.2142/biophysico.bppb-v20.0047
  • Bekker, GJ; Fukunishi, Y; Higo, J; Kamiya, N.
    Binding Mechanism of Riboswitch to Natural Ligand Elucidated by McMD-Based Dynamic Docking Simulations.
    ACS OMEGA. 2024 Jan 10;9(3):3412-3422. doi: 10.1021/acsomega.3c06826 eCollection
  • Germany, EM; Thewasano, N; Imai, K; Maruno, Y; Bamert, RS; Stubenrauch, CJ; Dunstan, RA; Ding, Y; Nakajima, Y; Lai, X; Webb, CT; Hidaka, K; Tan, KS; Shen, H; Lithgow, T; Shiota, T.
    Dual recognition of multiple signals in bacterial outer membrane proteins enhances assembly and maintains membrane integrity.
    ELIFE. 2024 Jan 16;12:RP90274. doi: 10.7554/eLife.90274
  • Shimizu, R; Murai, K; Tanaka, K; Sato, Y; Takeda, N; Nakasyo, S; Shirasaki, T; Kawaguchi, K; Shimakami, T; Nio, K; Nakaya, Y; Kagiwada, H Horimoto, K; Mizokami, M; Kaneko, S; Murata, K; Yamashita, T; Honda, M.
    Nucleos(t)ide analogs for hepatitis B virus infection differentially regulate the growth factor signaling in hepatocytes.
    HEPATOL COMMUN. 2024 Jan 5;8(1):e0351. doi: 10.1097/HC9.0000000000000351
  • Fukuda, I; Moritsugu, K; Higo, J; Fukunishi, Y.
    A cutoff-based method with charge-distribution-data driven pair potentials for efficiently estimating electrostatic interactions in molecular systems.
    J CHEM PHYS. 2023 Dec 21;159(23):234116. doi: 10.1063/5.0172270
  • Watanabe, Y; Iwasaki, Y; Sasaki, K; Motono, C; Imai, K; Suzuki, K.
    Atg15 is a vacuolar phospholipase that disintegrates organelle membranes.
    CELL REP. 2023 Dec 15:113567. doi: 10.1016/j.celrep.2023.113567
  • Maeda, F; Adachi, S; Natsume, T.
    Non-destructive and efficient method for obtaining miRNA information in cells by artificial extracellular vesicles.
    SCI REP. 2023 Dec 14;13(1):22231. doi: 10.1038/s41598-023-48995-5
  • Ohkawa, M; Konno, M.
    RNA Modification Related Diseases and Sensing Methods.
    APPLIED SCIENCES-BASEL. 2023 13(11) 6376. doi: 10.3390/app13116376
  • Shin, WH; Kumazawa, K; Imai, K; Hirokawa, T; Kihara, D.
    Quantitative comparison of protein-protein interaction interface using physicochemical feature-based descriptors of surface patches.
    FRONT MOL BIOSCI. 2023 Feb 6;10:1110567. doi: 10.3389/fmolb.2023.1110567
  • Takeda, H; Busto, JV; Lindau, C; Tsutsumi, A; Tomii, K; Imai, K; Yamamori, Y; Hirokawa, T; Motono, C; Ganesan, I; Wenz, LS; Becker, T; Kikkawa, M; Pfanner, N; Wiedemann, N; Endo, T.
    A multipoint guidance mechanism for β-barrel folding on the SAM complex.
    NAT STRUCT MOL BIOL. 2023 Jan 5. doi: 10.1038/s41594-022-00897-2
  • Hayashida, R; Kikuchi, R; Imai, K; Kojima, W; Yamada, T; Iijima, M; Sesaki, H; Tanaka, K; Matsuda, N; Yamano, K.
    Elucidation of ubiquitin-conjugating enzymes that interact with RBR-type ubiquitin ligases using a liquid-liquid phase separation-based method.
    J BIOL CHEM. 2022 Dec 20:102822. doi: 10.1016/j.jbc.2022.102822
  • Murotomi, K; Kagiwada, H; Hirano, K; Yamamoto, S; Numata, N; Matsumoto, Y; Kaneko, H; Namihira, M.
    Cyclo-glycylproline attenuates hydrogen peroxide-induced cellular damage mediated by the MDM2-p53 pathway in human neural stem cells.
    J CELL PHYSIOL. 2022 Dec 31. doi: 10.1002/jcp.30940
  • Fukunishi, Y; Higo, J; Kasahara, K.
    Computer simulation of molecular recognition in biomolecular system: from in silico screening to generalized ensembles.
    BIOPHYS REV. 2022 Nov 28:1-25. doi: 10.1007/s12551-022-01015-8
  • Lintuluoto, M; Abe, M; Horioka, Y; Fukunishi, Y; Tamura, H; M, Lintuluoto J.
    Investigation on substrate specificity and catalytic activity of serine protease neuropsin.
    BIOPHYS PHYSICOBIOL. 2022 Sep 22;19:e190040. doi: 10.2142/biophysico.bppb-v19.0040
  • Kagiwada, H; Motono, C; Horimoto, K; Fukui, K.
    Phosprof: pathway analysis database of drug response based on phosphorylation activity measurements.
    DATABASE (Oxford). 2022 Aug 22;2022:baac072. doi: 10.1093/database/baac072
  • Higo, J; Kasahara, K; Bekker, GJ; Ma, B; Sakuraba, S; Iida, S; Kamiya, N; Fukuda, I; Kono, H; Fukunishi, Y; Nakamura, H.
    Fly casting with ligand sliding and orientational selection supporting complex formation of a GPCR and a middle sized flexible molecule.
    SCI REP. 2022 Aug 13;12(1):13792. doi: 10.1038/s41598-022-17920-7
  • Hirata, Y; Oda, AH; Motono, C; Shiro, M; Ohta, K.
    Imputation-free reconstructions of three-dimensional chromosome architectures in human diploid single-cells using allele-specified contacts.
    SCI REP. 2022 Jul 11;12(1):11757. doi: 10.1038/s41598-022-15038-4
  • Kose, S; Imai, K; Watanabe, A; Nakai, A; Suzuki, Y; Imamoto, N.
    Lack of Hikeshi activates HSF1 activity under normal conditions and disturbs the heat-shock response.
    LIFE SCI ALLIANCE. 2022 May 17;5(9):e202101241. doi: 10.26508/lsa.202101241
  • Maeda, F; Kato, A; Takeshima, K; Shibazaki, M; Sato, R; Shibata,T; Miyake, K; Kozuka-Hata, H; Oyama, M; Shimizu, E; Imoto, S; Miyano, S; Adachi, S; Natsume, T; Takeuchi, K; Maruzuru, Y; Koyanagi, N; Jun, A; Yasushi, K.
    Role of the Orphan Transporter SLC35E1 in the Nuclear Egress of Herpes Simplex Virus 1.
    J VIROL. 2022 Apr 27:e0030622. doi: 10.1128/jvi.00306-22
  • Santos, HJ; Hanadate, Y; Imai, K; Watanabe, H; Nozaki, T.
    Entamoeba histolytica EHD1 Is Involved in Mitosome-Endosome Contact.
    MBIO. 2022 Apr 11:e0384921. doi: 10.1128/mbio.03849-21
  • Araiso, Y; Imai, K; Endo, T.
    Role of the TOM Complex in Protein Import into Mitochondria: Structural Views.
    ANNU REV BIOCHEM. 2022 Feb 14. doi: 10.1146/annurev-biochem-032620-104527
  • Ono, J; Koshimizu, U; Fukunishi, Y; Nakai, H.
    Multiple protonation states in ligand-free SARS-CoV-2 main protease revealed by large-scale quantum molecular dynamics simulations.
    CHEM PHYS LETT. 2022 Feb 22;794:139489. doi: 10.1016/j.cplett.2022.139489
  • Queliconi BB, Kojima W, Kimura M, Imai K, Udagawa C, Motono C, Hirokawa T, Tashiro S, Caaveiro JMM, Tsumoto K, Yamano K, Tanaka K, Matsuda N.
    Unfolding is the driving force for mitochondrial import and degradation of Parkinsons disease-related protein DJ-1.
    J CELL SCI. 2021 Oct 22:jcs.258653. doi: 10.1242/jcs.258653
  • Kimura, M; Imai, K; Morinaka, Y; Hosono-Sakuma, Y; Horton, P; Imamoto, N.
    Distinct mutations in importin-β family nucleocytoplasmic transport receptors transportin-SR and importin-13 affect specific cargo binding.
    SCI REP. 2021 Aug 2;11(1):15649. doi: 10.1038/s41598-021-94948-1
  • Motono, C; Yanagida, S; Sato, M; Hirokawa, T.
    MDContactCom: a tool to identify differences of protein molecular dynamics from two MD simulation trajectories in terms of interresidue contacts.
    BIOINFORMATICS. 2021 Jul 21:btab538. doi: 10.1093/bioinformatics/btab538
  • Iida, S; Fukunishi, Y.
    Asymmetric dynamics of dimeric SARS-CoV-2 and SARS-CoV main proteases in an apo form: Molecular dynamics study on fluctuations of active site, catalytic dyad, and hydration water.
    BBA ADV. 2021;1:100016. doi: 10.1016/j.bbadva.2021.100016. Epub 2021 Jun 20
  • Kagiwada, H; Kiboku, T; Matsuo, H; Kitazawa, M; Fukui, K; Horimoto, K.
    Assessing the activation/inhibition of tyrosine kinase-related pathways with a newly developed platform.
    PROTEOMICS. 2021 Jun 21:e2000251. doi: 10.1002/pmic.202000251
  • Moritsugu, K; Takeuchi, K; Kamiya, N; Higo, J; Yasumatsu, I; Fukunishi, Y; Fukuda, I.
    Flexibility and Cell Permeability of Cyclic Ras-Inhibitor Peptides Revealed by the Coupled Nosé-Hoover Equation.
    J CHEM INF MODEL. 2021 Apr 9. doi: 10.1021/acs.jcim.0c01427
  • Lintuluoto, M; Horioka, Y; Hongo, S; Lintuluoto, JM; Fukunishi, Y.
    Molecular Dynamics Simulation Study on Allosteric Regulation of CD44-Hyaluronan Binding as a Force Sensing Mechanism.
    ACS OMEGA. 2021 Mar 16;6(12):8045-8055. doi: 10.1021/acsomega.0c05502. eCollection

▲ back to top