Biological Data Science Research Group

Research Project

We are working on research to understand the molecular mechanism of disease onset and patient stratification for early diagnosis, based on analysis of multimodal data integrating of multi-layer omics data and diagnostic imaging data. Also, we are verifying hypothesis obtained from the multimodal data analysis using real-world data such as data of health insurance claim.

Research Project

RNA/DNA is attracting attention as a new drug discovery modality. Theoretical calculation technology for nucleic acids is underdeveloped compared to proteins, and the accuracy and reliability are unknown. We have reconstructed the computational technology that we have cultivated jointly with more than 40 pharmaceutical and IT companies in Japan for nucleic acids, implemented it in the drug discovery software group myPresto, We develop and provide theoretical tools to elucidate mutual recognition mechanisms.

Research Project

RNA modifications are known to be changed in various diseases. However, the measurement technology is still in development, and the application to diagnosis and treatment has not yet been realized. Therefore, we are developing a new technology to measure modification information of omics, especially RNA. We are also analyzing the modification information to develop early diagnosis technology and new treatment methods for various diseases, including cancer.

Research Project

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 porotein 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 using mixed solvent molecular dynamics simulation.

Research Project

Various kinds of molecules consist of cells, and they transmit information to determine the cellular state. In this research, we are developing technologies to elucidate precisely how the molecular network alters accompanied by cell differentiation and adaptation to the extracellular environment, and how the changes of the network affect the cellular state. Through these studies, we promote highly accurate regulation of differentiation in pluripotent stem cells.

Research Project

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.

Research Project

The herpes simplex virus 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 kbp, and (3) the wide host range of vector transduction. We are currently working on the methods for the efficient vector production and retargeting of HSV vectors. We are also working on using viral vectors for advanced cell control and non-destructive acquisition of molecular information from disease model cell lines to search for molecular information (biomarkers) suitable for minimally invasive diagnosis of diseases and candidate therapeutic targets.

Results

• 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
• Kato, K; Okazaki, S; Schmitt-Ulms, C; Jiang, K; Zhou, W; Ishikawa, J; Isayama, Y; Adachi, S; Nishizawa, T; Makarova, KS; Koonin, EV; Abudayyeh, OO; Gootenberg, JS; Nishimasu, H.
  RNA-triggered protein cleavage and cell growth arrest by the type III-E CRISPR nuclease-protease.
  SCIENCE. 2022 Nov 25;378(6622):882-889. doi: 10.1126/science.add7347
• 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
• Tirta, YK; Adachi, S; Perez, CAG; Adhitama, N; Nong, QD; Natsume, T; Kato, Y; Watanabe, H.
  CELF1 represses Doublesex1 expression via its 5 UTR in the crustacean Daphnia magna.
  PLOS ONE. 2022 Oct 14;17(10):e0275526. doi: 10.1371/journal.pone.0275526
• Sato, R; Suzuki, K; Yasuda, Y; Suenaga, A; Fukui, K.
  RNAapt3D: RNA aptamer 3D-structural modeling database.
  BIOPHYS J. 2022 Sep 22:S0006-3495(22)00773-1. doi: 10.1016/j.bpj.2022.09.023
• Li, S; Ikeuchi, K; Kato, M; Buschauer, R; Sugiyama, T; Adachi, S; Kusano, H; Natsume, T; Berninghausen, O; Matsuo, Y; Becker, T; Beckmann, R; Inada, T.
  Sensing of individual stalled 80S ribosomes by Fap1 for nonfunctional rRNA turnover.
  MOL CELL. 2022 Sep 15;82(18):3424-3437.e8. doi: 10.1016/j.molcel.2022.08.018
• 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
• 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
• 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
• Amemiya, T; Horimoto, K; Fukui, K.
  Application of multiple omics and network projection analyses to drug repositioning for pathogenic mosquito-borne viruses.
  SCI REP. 2021 May 12;11(1):10136. doi: 10.1038/s41598-021-89171-x
• Kohrogi, K; Hino, S; Sakamoto, A; Anan, K; Takase, R; Araki, H; Hino, Y; Araki, K; Sato, T; Nakamura, K; Nakao, M
  LSD1 defines erythroleukemia metabolism by controlling the lineage-specific transcription factors GATA1 and C/EBP
  Blood Adv. 2021 May 11;5(9):2305-2318. doi: 10.1182/bloodadvances.2020003521
• Ohashi, H; Watashi, K; Saso, W; Shionoya, K; Iwanami, S; Hirokawa, T; Shirai, T; Kanaya, S; Ito, Y; Kim, KS; Nomura, T; Suzuki, T; Nishioka, K; Ando, S; Ejima, K; Koizumi, Y; Tanaka, T; Aoki, S; Kuramochi, K; Suzuki, T; Hashiguchi, T; Maenaka, K; Matano, T; Muramatsu, M; Saijo, M; Aihara, K; Iwami, S; Takeda, M; McKeating, JA; Wakita, T
  Potential anti-COVID-19 agents, Cepharanthine and Nelfinavir, and their usage for combination treatment.
  ISCIENCE. 2021 Mar 26:102367. doi: 10.1016/j.isci.2021.102367
• Koiwai K, Morohashi K, Inaba K, Ebihara K, Kojima H, Okabe T, Yoshino R, Hirokawa T, Nampo T, Fujikawa Y, Inoue H, Yumoto F, Senda T, Niwa R
  Non-steroidal inhibitors of Drosophila melanogaster steroidogenic glutathione S-transferase Noppera-bo
  J Pestic Sci. 2021 Feb 20;46(1):75-87. doi: 10.1584/jpestics.D20-072
• Kojima W, Yamano K, Kosako H, Imai K, Kikuchi R, Tanaka K, Matsuda N
  Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy.
  AUTOPHAGY. 2021 Jan 26:1-26. doi: 10.1080/15548627.2021.1874133
• Takeda H, Tsutsumi A, Nishizawa T, Lindau C, Busto JV, Wenz LS, Ellenrieder L, Imai K, Straub SP, Mossmann W, Qiu J, Yamamori Y, Tomii K, Suzuki J, Murata T, Ogasawara S, Nureki O, Becker T, Pfanner N, Wiedemann N, Kikkawa M, Endo T
  Mitochondrial sorting and assembly machinery operates by β-barrel switching.
  NATURE. 2021 Jan 6. doi: 10.1038/s41586-020-03113-7
• Sasaki S, Ma Y, Ishizuka T, Bao HL, Hirokawa T, Xu Y, Tera M, Nagasawa K
  Linear consecutive hexaoxazoles as G4 ligands inducing chair-type anti-parallel topology of a telomeric G-quadruplex.
  RSC ADVANCES 10 (71) 43319-43323; doi: 10.1039/d0ra09413g DEC 7
• Imai K, Nakai K
  Tools for the Recognition of Sorting Signals and the Prediction of Subcellular Localization of Proteins From Their Amino Acid Sequences.
  FRONT GENET 2020 Nov 25;11:607812. doi: 10.3389/fgene.2020.607812. eCollection
• Sakamoto K, Masutani T, Hirokawa T
  Generation of KS-58 as the first K-Ras(G12D)-inhibitory peptide presenting anti-cancer activity in vivo.
  SCI REP. 10(1):21671 (2020) doi: 10.1038/s41598-020-78712-5
• Araiso Y, Imai K, Endo T
  Structural snapshot of the mitochondrial protein import gate
  FEBS J. 2020 Dec 10. doi: 10.1111/febs.15661
• Shin WH, Kumazawa K, Imai K, Hirokawa T, Kihara D
  Current Challenges and Opportunities in Designing Protein-Protein Interaction Targeted Drugs
  Adv Appl Bioinform Chem. 2020 Nov 12;13:11-25. doi: 10.2147/AABC.S235542
• Nguyen HN, Suzuki K, Kimura Y, Hirokawa T, Murakami-Tonami Y, Abe H
  SYNTHESIS AND BIOLOGICAL EVALUATION OF NMDI14 DERIVATIVES AS ANTI-MESOTHELIOMA AGENTS
  HETEROCYCLES 100 (2) 253-266; (2020) doi: 10.3987/COM-19-14191
• Santos HJ, Chiba Y, Makiuchi T, Arakawa S, Murakami Y, Tomii K, Imai K, Nozaki T
  Import of Entamoeba histolytica Mitosomal ATP Sulfurylase Relies on Internal Targeting Sequences
  Microorganisms. 8(8):1229. (2020) doi: 10.3390/microorganisms8081229
• Nakagita T, Taketani C, Narukawa M, Hirokawa T, Kobayashi T, Misaka T
  Ibuprofen, a nonsteroidal anti-inflammatory drug, is a potent inhibitor of the human sweet taste receptor
  Chem Senses. bjaa057 (2020) doi: 10.1093/chemse/bjaa057
• Tomonari T, Sato Y, Tanaka H, Tanaka T, Fujino Y, Mitsui Y, Hirao A, Taniguchi T, Okamoto K, Sogabe M, Miyamoto H, Muguruma N, Kagiwada H, Kitazawa M, Fukui K, Horimoto K, Takayama T
  Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence and in vitro assessment via protein phosphorylation array
  Oncotarget. 11: 2531-2542 (2020) doi: 10.18632/oncotarget.27640
• Manabe T, Yasuda H, Terai H, Kagiwada H, Hamamoto J, Ebisudani T, Kobayashi K, Masuzawa K, Ikemura S, Kawada I, Hayashi Y, Fukui K, Horimoto K, Fukunaga K, Soejima K
  IGF2 Autocrine-Mediated IGF1R Activation Is a Clinically Relevant Mechanism of Osimertinib Resistance in Lung Cancer
  Molecular Cancer Res. 18: 549-559 (2020) doi: 10.1158/1541-7786.MCR-19-0956
• Koiwai K, Inaba K, Morohashi K, Enya S, Arai R, Kojima H, Okabe T, Fujikawa Y, Inoue H, Yoshino R, Hirokawa T, Kato K, Fukuzawa K, Shimada-Niwa Y, Nakamura A, Yumoto F, Senda T, Niwa R
  An integrated approach to unravel a crucial structural property required for the function of the insect steroidogenic Halloween protein Noppera-bo
  J Biol Chem. 0: 0 (2020) doi: 10.1074/jbc.RA119.011463
• Kagamu H, Kitano S, Yamaguchi O, Yoshimura K, Horimoto K, Kitazawa M, Fukui K, Shiono A, Mouri A, Nishihara F, Miura Y, Hashimoto K, Murayama Y, Kaira K, Kobayashi K
  CD4(+) T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy
  Cancer Immunology Res. 8 8: 334-344 (2020) doi: 10.1158/2326-6066.CIR-19-0574
• Adachi K, Yamada T, Ishizuka H, Oki M, Tsunogae S, Shimada N, Chiba O, Orihara T, Hidaka M, Hirokawa T, Odagi M, Konoki K, Yotsu-Yamashita M, Nagasawa K
  Synthesis of C12-Keto Saxitoxin Derivatives with Unusual Inhibitory Activity Against Voltage-Gated Sodium Channels
  Chemistry. 26: 2025-2033 (2020) doi: 10.1002/chem.201904184
• Kitazawa M, Hatta T, Sasaki Y,Fukui K, Ogawa K, Fukuda E, Goshima N, Okita N, Yamada Y, Nakagama H,Natsume T, Horimoto K
  Promotion of the Warburg effect is associated with poor benefit from adjuvant chemotherapy in colorectal cancer
  Cancer Sci. 111: 658-666 (2020) doi: 10.1111/cas.14275
• Chiba S, Ohue M, Gryniukova A, Borysko P, Zozulya S, Yasuo N, Yoshino R, Ikeda K, Shin WH, Kihara D, Iwadate M, Umeyama H, Ichikawa T, Teramoto R, Hsin KY, Gupta V, Kitano H, Sakamoto M, Higuchi A, Miura N, Yura K, Mochizuki M, Ramakrishnan C, Thangakani AM, Velmurugan D, Gromiha MM, Nakane I, Uchida N, Hakariya H, Tan M, Nakamura HK, Suzuki SD, Ito T, Kawatani M, Kudoh K, Takashina S, Yamamoto KZ, Moriwaki Y, Oda K, Kobayashi D, Okuno T, Minami S, Chikenji G, Prathipati P, Nagao C, Mohsen A, Ito M, Mizuguchi K, Honma T, Ishida T, Hirokawa T, Akiyama Y, Sekijima M
  A prospective compound screening contest identified broader inhibitors for Sirtuin 1
  Sci Rep. 9: 19585 (2019) doi: 10.1038/s41598-019-55069-y
• Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnewski M, Schutze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo T
  Structure of the mitochondrial import gate reveals distinct preprotein paths
  Nature.575: 395-401 (2019) doi: 10.1038/s41586-019-1680-7
• Shiba-Ishii A, Hong J, Hirokawa T, Kim Y, Nakagawa T, Sakashita S, , Sakamoto N, Kozuma Y, Sato Y, Noguchi M
  Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis
  Clinical Cancer Res. 25: 2809-2820 (2019) doi: 10.1158/1078-0432.CCR-18-3631
• Yamasaki S, Amemiya T, Yabuki Y, Horimoto K, Fukui K^＊
  ToGo-WF: prediction of RNA tertiary structures and RNA-RNA/protein interactions using the KNIME workflow
  J. Computer-Aided Molecular Design 33: 497-507 (2019) doi: 10.1007/s10822-019-00195-y
• Santos HJ, Imai K, Makiuchi T, Tomii K, Horton P, Nozawa A, Okada K, Tozawa Y, Nozaki T
  Novel lineage-specific transmembrane beta-barrel proteins in the endoplasmic reticulum of Entamoeba histolytica
  FEBS J. 65: 164-170 (2019) doi: 10.1111/febs.14870
• Yamada K, Nakazawa M, Matsumoto K, Tagami U, Hirokawa T, Homma K, Mori S, Matsumoto R, Saikawa W, Kitajima S
  Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3
  Acs Medicinal Chemistry Letters10: 800-805 (2019) doi: 10.1021/acsmedchemlett.9b00051
• Santos HJ, Hanadate Y, Imai K, Nozaki T
  An Entamoeba-Specific Mitosomal Membrane Protein with Potential Association to the Golgi Apparatus
  Genes 10: 10 (2019) doi: 10.3390/genes10050367
• Shawki HH, Ishikawa-Yamauchi Y, Kawashima A, Katoh Y, Matsuda M, Al-Soudy AS, Minisy FM, Kuno A, Gulibaikelamu X, Hirokawa T, Takahashi S, Oishi H
  EFCAB2 is a novel calcium-binding protein in mouse testis and sperm
  PloS One. 14: 0 (2019) doi: 10.1371/journal.pone.0214687
• Parasuraman P, Selvin JFA, Gromiha MM, Fukui K, Veluraja K
  Investigation on the binding specificity of Agrocybe cylindracea galectin towards alpha(2,6)-linked sialyllactose by molecular modeling and molecular dynamics simulations
  J. Carbohydrate Chemistry 250: 463-473 (2019) doi: 10.1080/07328303.2019.1631323
• Nakagita T, Ishida A, Matsuya T, Kobayashi T, Narukawa M, Hirokawa T, Hashimoto M, Misaka T
  Structural insights into the differences among lactisole derivatives in inhibitory mechanisms against the human sweet taste receptor
  PloS One. 14: 0 (2019) doi: 10.1371/journal.pone.0213552
• Sakaue H, Shiota T, Ishizaka N, Kawano S, Tamura Y, Tan KS, Imai K, Motono C, Hirokawa T, Taki K, Miyata N, Kuge O, Lithgow T, Endo T
  Porin Associates with Tom22 to Regulate the Mitochondrial Protein Gate Assembly
  Mol Cell. 73: 1044-1055 (2019) doi: 10.1016/j.molcel.2019.01.003
• Yasuda S, Hayashi T, Kajiwara Y, Murata T, Kinoshita M
  Analyses based on statistical thermodynamics for large difference between thermophilic rhodopsin and xanthorhodopsin in terms of thermostability
  J. Chemical Physics 150: 10 (2019) doi: 10.1063/1.5082217
• Amemiya T, Gromiha MM, Horimoto K, Fukui K^＊
  Drug repositioning for dengue haemorrhagic fever by integrating multiple omics analyses
  Scientific Reports 0: 0 (2019) doi: 10.1038/s41598-018-36636-1
• Toyoda Y, Morimoto K, Suno R, Horita S, Yamashita K, Hirata K, Sekiguchi Y, Yasuda S, Shiroishi M, Shimizu T, Urushibata Y, Kajiwara Y, Inazumi T, Hotta Y, Asada H, Nakane T, Shiimura Y, Nakagita T, Tsuge K, Yoshida S, Kuribara T, Hosoya T, Sugimoto Y, Nomura N, Sato M, Hirokawa T, Kinoshita M, Murata T, Takayama K, Yamamoto M, Narumiya S, Iwata S, Kobayashi T
  Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface
  Nat Chem Biol. 15: 18-26 (2019) doi: 10.1038/s41589-018-0131-3
• Ma Y, Iida K, Sasaki S, Hirokawa T, Heddi B, Phan AT, Nagasawa K
  Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains
  Molecules. 24: 0 (2019) doi: 10.3390/molecules24020263
• Ohsawa K, Yoshida M, Izumikawa M, Takagi M, Shin-Ya K, Goshima N, Hirokawa T, Natsume T, Doi T
  Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer
  Bioorg Med Chem. 10: 185 (2018) doi: 10.1016/j.bmc.2018.11.001
• Nagai T, Mukoyama S, Kagiwada H, Goshima N, Mizuno K
  Cullin-3-KCTD10-mediated CEP97 degradation promotes primary cilium formation
  J Cell Sci. 131: 0 (2018) doi:10.1242/jcs.219527
• Ma Y, Tsushima Y, Sakuma M, Sasaki S, Iida K, Okabe S, Seimiya H, Hirokawa T, Nagasawa K
  Development of G-quadruplex ligands for selective induction of a parallel-type topology
  Org Biomol Chem. 0: 0 (2018) doi: 10.1039/c8ob01702f
• Toda Y, Nakagita T, Hirokawa T, Yamashita Y, Nakajima A, Narukawa M, Ishimaru Y, Uchida R, Misaka T
  Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional
  Sci Rep. 8: 11796 (2018) doi: 10.1038/s41598-018-30315-x
• Nakagita T, Ishida A, Kobayashi T, Hirokawa T, Hashimoto M, Misaka, T
  How do sweet taste inhibitors having the O-phenyllactic acid skeleton interact with transmembrane domain of T1R3
  Chemical Senses 43: (5):E137-E137; JUN 2018 doi: 10.1093/chemse/bjy010
• Kawamura S, Ito Y, Hirokawa T, Hikiyama E, Yamada S, Shuto S
  Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
  J Med Chem. 61: 4020-4029 (2018) doi: 10.1021/acs.jmedchem.8b00041
• Nemoto K, Kagawa M, Nozawa A, Hasegawa Y, Hayashi M, Imai K, Tomii K, Sawasaki T
  Identification of new abscisic acid receptor agonists using a wheat cell-free based drug screening system
  Sci Rep. 8: 4268 (2018) doi: 10.1038/s41598-018-22538-9
• Caba C, Khan HA, Auld J, Ushioda R, Araki K, Nagata K, Mutus B
  Conserved Residues Lys(57 )and Lys(401) of Protein Disulfide Isomerase Maintain an Active Site Conformation for Optimal Activity: Implications for Post-Translational Regulation
  Frontiers In Molecular Biosciences 9: 92-100 (2018) doi: 10.3389/fmolb.2018.00018
• Kitamura A, Ishida Y, Kubota H, Pack CG, Homma T, Ito S, Araki K, Kinjo M, Nagata K
  Detection of substrate binding of a collagen-specific molecular chaperone HSP47 in solution using fluorescence correlation spectroscopy
  Biochem.... And Biophysical Res. Communications 497: 279-284 (2018) doi: 10.1016/j.bbrc.2018.02.069
• Kasahara K, Aoki H, Kiyono T, Wang S, Kagiwada H, Yuge M, Tanaka T, Nishimura Y, Mizoguchi A, Goshima N, Inagaki M
  EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase
  Nat Commun. 9: 758 (2018) doi: 10.1038/s41467-018-03117-y
• Sakai Y, Kawaguchi A, Nagata K, Hirokawa T
  Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers
  Microbiol Immunol. 62: 34-43 (2018) doi: 10.1111/1348-0421.12561
• Suno R, Kimura KT, Nakane T, Yamashita K, Wang J, Fujiwara T, Yamanaka Y, Im D, Horita S, Tsujimoto H, Tawaramoto MS, Hirokawa T, Nango E, Tono K, Kameshima T, Hatsui T, Joti Y, Yabashi M, Shimamoto K, Yamamoto M, Rosenbaum DM, Iwata S, Shimamura T, Kobayashi T
  Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA
  Structure. 26: 7-19 (2018) doi: 10.1016/j.str.2017.11.005
• Ito S, Ogawa K, Takeuchi K, Takagi M, Yoshida M, Hirokawa T, Hirayama S, Shin-ya K, Shimada I, Doi T, Goshima N, Natsume T, Nagata K
  A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis
  J. Biol. Chem. 292: 20076-20085 (2017) doi: 10.1074/jbc.M117.815936
• Nemoto K, Ramadan A, Arimura GI, Imai K, Tomii K, Shinozaki K, Sawasaki T
  Tyrosine phosphorylation of the GARU E3 ubiquitin ligase promotes gibberellin signalling by preventing GID1 degradation
  Nat Commun. 8: 1004 (2017) doi: 10.1038/s41467-017-01005-5
• Chiba S, Ishida T, Ikeda K, Mochizuki M, Teramoto R, Taguchi YH, Iwadate M, Umeyama H, Ramakrishnan C, Thangakani AM, Velmurugan D, Gromiha MM, Okuno T, Kato K, Minami S, Chikenji G, Suzuki SD, Yanagisawa K, Shin WH, Kihara D, Yamamoto KZ, Moriwaki Y, Yasuo N, Yoshino R, Zozulya S, Borysko P, Stavniichuk R, Honma T, Hirokawa T, Akiyama Y, Sekijima M
  An iterative compound screening contest method for identifying target protein inhibitors using the tyrosine-protein kinase Yes
  Sci Rep. 7: 12038 (2017) doi:10.1038/s41598-017-10275-4
• Okamoto N, Mizote K, Honda H, Saeki A, Watanabe Y, Yamaguchi-Miyamoto T, Fukui R, Tanimura N, Motoi Y, Akashi-Takamura S, Kato T, Fujishita S, Kimura T, Ohto U, Shimizu T, Hirokawa T, Miyake K, Fukase K, Fujimoto Y, Nagai Y, Takatsu K
  Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex
  J. Biol. Chem. 292: 15378-15394 (2017) doi: 10.1074/jbc.M117.791780
• Shinohara Y, Koyama YM, Ukai-Tadenuma M, Hirokawa T, Kikuchi M, Yamada RG, Ukai H, Fujishima H, Umehara T, Tainaka K, Ueda HR
  Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock
  Mol. Cell 67: 783- (2017) doi: 10.1016/j.molcel.2017.08.009
• Shiga Y, Murata D, Sugimoto A, Oshima Y, Tada M, Ishii-Watabe A, Imai K, Tomii K, Takeuchi T, Kagaya S, Sato A
  Hinge-Deficient IgG1 Fc Fusion: Application to Human Lactoferrin
  Mol Pharm. 14: 3025-3035 (2017) doi: 10.1021/acs.molpharmaceut.7b00221
• Fukasawa Y, Oda T, Tomii K, Imai K^*
  Origin and Evolutionary Alteration of the Mitochondrial Import System in Eukaryotic Lineages
  Mol Biol Evol. 34: 1574-1586 (2017) doi: 10.1093/molbev/msx096
• Sayama M, Inoue A, Nakamura S, Jung SJ, Ikubo M, Otani Y, Uwamizu A, Kishi T, Makide K, Aoki J, Hirokawa T, Ohwada T
  Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis
  J. Med. Chem. 60: 6384-6399 (2017) doi: 10.1021/acs.jmedchem.7b00693
• Uegaki K, Kumanogoh H, Mizui T, Hirokawa T, Ishikawa Y, Kojima M
  BDNF Binds Its Pro-Peptide with High Affinity and the Common Val66Met Polymorphism Attenuates the Interaction
  Int J Mol Sci. 18: 0 (2017) doi: 10.3390/ijms18051042
• Asamitsu K, Hirokawa T, Okamoto T
  MD simulation of the Tat/Cyclin T1/CDK9 complex revealing the hidden catalytic cavity within the CDK9 molecule upon Tat binding
  PloS One. 12: 0 (2017) doi: 10.1371/journal.pone.0171727
• Wada Y, Nakano S, Morimoto A, Kasahara K, Hayashi T, Takada Y, Suzuki H, Niwa-Sakai M, Ohashi S, Mori M, Hirokawa T, Shuto S
  Discovery of Novel Indazole Derivatives as Orally Available beta(3)-Adrenergic Receptor Agonists Lacking Off-Target-Based Cardiovascular Side Effects
  J. Med. Chem. 60: 3252-3265 (2017) doi: 10.1021/acs.jmedchem.6b01197