分子シミュレーションチーム

研究詳細 : 重点課題

担当:広川 貴次 研究チーム長

研究テーマ

  • ■ 創薬標的タンパク質を対象にした、タンパク質立体構造モデリング、タンパク質-リガンドドッキングおよびタンパク質-タンパク質相互作用解析
  • ■ タンパク質立体構造情報に基づく医薬分子設計、ケモインフォマティクス
  • ■ タンパク質立体構造予測システムの開発
  • ■ 分子動力学計算の高精度化のための基盤研究
  • ■ 分子動力学計算によるタンパク質折りたたみ形成シミュレーションやアミロイドペプチド凝集メカニズムの解析
  • ■ 民間企業等との共同研究を通じたインシリコスクリーニングによる医薬品候補化合物の探索と最適化析


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研究成果、論文リスト等

2018
Analysis by metadynamics simulation of binding pathway of influenza virus M2 channel blockers.
Microbiol Immunol. 2018 Jan;62(1):34-43.
Sakai Y, Kawaguchi A, Nagata K, Hirokawa T.

Crystal Structures of Human Orexin 2 Receptor Bound to the Subtype-Selective Antagonist EMPA Structure.
2018 Jan 2;26(1):7-19
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.

2017
Discovery of Novel Indazole Derivatives as Orally Available β3-Adrenergic Receptor Agonists Lacking Off-Target-Based Cardiovascular Side Effects.
J Med Chem. 2017 Apr 27;60(8):3252-3265.
Wada Y, Nakano S, Morimoto A, Kasahara KI, Hayashi T, Takada Y, Suzuki H, Niwa-Sakai M, Ohashi S, Mori M, Hirokawa T, Shuto S

BDNF Binds Its Pro-Peptide with High Affinity and the Common Val66Met Polymorphism Attenuates the Interaction.
Int J Mol Sci. 2017 May 12;18(5)
Uegaki K, Kumanogoh H, Mizui T, Hirokawa T, Ishikawa Y, Kojima M

Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis.
J Med Chem. 2017 Jul 27;60(14):6384-6399.
Sayama M, Inoue A, Nakamura S, Jung S, Ikubo M, Otani Y, Uwamizu A, Kishi T, Makide K, Aoki J, Hirokawa T, Ohwada

Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.
J Biol Chem. 2017 Sep 15;292(37):15378-15394.
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

Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock.
Mol Cell. 2017 Sep 7;67(5):783-798
Shinohara Y, Koyama YM, Ukai-Tadenuma M, Hirokawa T, Kikuchi M, Yamada RG, Ukai H, Fujishima H, Umehara T, Tainaka K, Ueda HR.

An iterative compound screening contest method for identifying target protein inhibitors using the tyrosine-protein kinase Yes.
Sci Rep. 2017 Sep 20;7(1):12038
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

A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis.
J Biol Chem. 2017 Dec 8;292(49):20076-20085.
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.

2015
NovelpH-dependent regulation of human cytosolic sialidase2 (NEU2) activities by siastatin B and structural prediction of NEU2/siastatin B complex
Biochem. Biophys. Rep., 2015, 4, 234-242.
Rahman M.M, Hirokawa T, Tsuji D, Tsukimoto J, Hitaoka S, Yoshida T, Chuman H, Itoh K

Privacy-preserving search for chemical compound databases
BMC Bioinformatics, 2015, 16 Suppl 18, S6.
Shimizu K, Nuida K, Arai H, Mitsunari S, Attrapadung N, Hamada M, Tsuda K, Hirokawa T, Sakuma J, Hanaoka G, Asai K

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target
Sci. Rep., 2015, 5, 17209
Chiba S, Ikeda K, Ishida T, Gromiha MM, Taguchi YH, Iwadate M, Umeyama H, Hsin KY, Kitano H, Yamamoto K, Sugaya N, Kato K, Okuno T, Chikenji G, Mochizuki M, Yasuo N, Yoshino R, Yanagisawa K, Ban T, Teramoto R, Ramakrishnan C, Thangakani AM, Velmurugan D, Prathipati P, Ito J, Tsuchiya Y, Mizuguchi K, Honma T, Hirokawa T, Akiyama Y, Sekijima M.

Design and synthesis of a berberine dimer: a fluorescent ligand with high affinity towards G-quadruplexes
Chemistry, 2015, 21, 14519-14528.
Tera M, Hirokawa T, Okabe S, Sugahara K, Seimiya H, Shimamoto K

Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation
J. Biol. Chem., 2015, 290, 25199-25211.
Yamano K, Queliconi BB, Koyano F, Saeki Y, Hirokawa T, Tanaka K, Matsuda N

Relationship between Human Evolution and Neurally Mediated Syncope Disclosed by the Polymorphic Sites of the Adrenergic Receptor Gene α2B-AR
PLoS One, 2015, 10(4), e0120788.
Komiyama T, Hirokawa T, Sato K, Oka A, Kamiguchi H, Nagata E, Sakura H, Otsuka K, Kobayashi H

Molecular dynamics simulation and experimental verification of the interaction between cyclin T1 and HIV-1 Tat proteins
PLoS One, 2015, 10(3), e0119451.
Asamitsu K, Hirokawa T, Hibi Y, Okamoto T.

2012
Trichostatin Analogues JBIR-109, JBIR-110, and JBIR-111 from the Marine Sponge-Derived Streptomyces sp. RM72.
Journal of natural products, 75(2) pp.285-9(2012).
Hosoya, T., Hirokawa, T., Takagi, M., Shin-Ya, K.

Cyclopropane-based stereochemical diversity-oriented conformational restriction strategy: histamine H3 and/or H4 receptor ligands with the 2,3-methanobutane backbone.
Organic & Biomolecular Chemistry, 10(4) pp.736-745(2012).
Watanabe, M., Kobayashi, T., Hirokawa, T., Yoshida, A., Ito, Y., Yamada, S., Orimoto, N., Yamasaki, Y., Arisawa, M., Shuto, S.

2011
Computational analysis of ligand recognition mechanisms by prostaglandin E2 (subtype 2) and D2 receptors."
Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta), 130, pp.1131-1143(2011).
Daiyasu, H., Hirokawa, T., Kamiya, N., Toh, H.

Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes.
BMC Bioinformatics, 11, pp.236(2010).
Uchikoga, N., Hirokawa, T.

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