ホーム＞企業・大学・研究機関のみなさまへ＞チームの紹介＞3D分子設計チーム＞研究詳細
3D分子設計チーム
重点課題1 重点課題2
研究詳細 ： 重点課題1
担当：福西 快文 研究チーム長
当チームでは理論計算による研究も行っています。
蛋白質のモデリング、蛋白質複合体のモデリング、分子動力学シミュレーション、自由エネルギー計算などの手法の開発に加え、 医薬品探索のための化合物データベースの構築手法、蛋白質―化合物ドッキングソフト、薬物スクリーニング手法の開発と、実証計算・実験を行っています。
私たちの研究成果は、分子シミュレーションソフトウェアシステム「myPresto」として、一般に無償公開しています。
「myPresto」は、市販化合物など数百万の化合物の立体構造のデータベース、それを元に、標的蛋白質構造ないし活性化合物情報を利用して 薬物スクリーニングを行うスクリーニングシステム、蛋白質―化合物ドッキングソフト、化合物のモデリングソフト、蛋白質の分子シミュレーションソフトなど 数十のソフトウェアとデータベースからなるシステムです。
myPrestoダウンロードサイト
（大阪大学蛋白質研究所付属プロテオミクス総合研究センター）
http://presto.protein.osaka-u.ac.jp/myPresto4/
最近の主な成果
・生理活性ペプチドから低分子医薬品を開発するインシリコ・ペプチドミメティクス技術開発
研究成果、論文リスト等
| 2016 |
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Miscellaneous topics in computer-aided drug design: Synthetic accessibility and GPU computing, and other topics. Current pharmaceutical design 2016, 22 (23), 3555-3568 Y. Fukunishi, T. Mashimo, K. Misoo, Y. Wakabayashi, T. Miyaki, S Ohta, M. Nakamura, K. Ikeda. |
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Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling. Journal of Computational Chemistry 2016, 37 (31), 2687-2700 S. Iida, T. Mashimo, T. Kurosawa, H. Hojo, H. Muta, Y. Goto, Y. Fukunishi, H. Nakamura, J. Higo. |
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Quantitative Structure‐activity Relationship (QSAR) Models for Docking Score Correction. Molecular Informatics (in press). Y. Fukunishi, S. Yamasaki, I. Yasumatsu, K. Takeuchi, T. Kurosawa, H. Nakamura. |
| 2015 |
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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method. J. Chem. Inf. Model.2015, 55 (9) 1936-1943. N. Hung, T. Tien, Y. Fukunishi, J. Higo, H. Nakamura, L. Le |
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Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform. J. Toxicol. Sci.2015, 40 (2) 223-233. H. Okazaki, S. Takeda, E. Ikeda, Y. Fukunishi, H. Ishii, A. Taniguchi, M. Tokuyasu, T. Himeno, K. Kakizo, K. Matsumoto, M. Shindo, H. Aramaki. |
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Virtual-system coupled adaptive umbrella sampling to compute free-energy landscape for flexible molecular docking. J. Comput. Chem.2015, 36 (20) 1489-1501. J. Higo, B. Dasgupta, T. Mashimo, Y. Fukunishi, H. Nakamura |
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Structure-Based Development of a Protein-Protein Interaction Inhibitor Targeting Tumor Necrosis Factor Receptor-Associated Factor 6. J Med Chem, 58, 5674-5683, (2015). Moriya J, Takeuchi K, Tai K, Arai K, Kobayashi N, Yoneda N, Fukunishi Y, Inoue A, Kihara M, Murakami T, Chiba K, Shimada I. |
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A Potent and Site-Selective Agonist of TRPA1. J. Am. Chem. Soc. 137, 15859-15864. (2015) Takaya, J., Mio, K., Shiraishi, T., Kurokawa, T., Otsuka, S., Mori, Y., and Uesugi, M. |
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Observation of tissues in open aqueous solution by atmospheric scanning electron microscopy: applicability to intraoperative cancer diagnosis. Int J Oncol. 46:1872-1882. (2015) Memtily N, Okada T, Ebihara T, Sato M, Kurabayashi A, Furihata M, Suga M, Nishiyama H, Mio K, Sato C. |
| 2014 |
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Structural insights into the function of a thermostable copper-containing nitrite reductase. Biochem. 2014 Feb;155(2):123-35. doi: 10.1093/jb/mvt107 Fukuda Y, Tse KM, Lintuluoto M, Fukunishi Y, Mizohata E, Matsumura H, Takami H, Nojiri M, Inoue |
| 2013 |
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Molecular dynamics simulations accelerated by GPU for biological macromolecules with a
non-Ewald scheme for electrostatic interactions. Journal of Chemical Theory and Computation. 9 (12) 5599-5609 (2013). T. Mashimo, Y. Fukunishi, N. Kamiya, Y. Takano, I. Fukuda, and H. Nakamura. |
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Molecular modeling of vasopressin receptor and in silico screening of V1b receptor
antagonists. Expert Opin Drug Discov. 2013 Aug;8(8):951-64.doi:10.1517/17460441.2013.799134. Hagiwara Y, Ohno K, Kamohara M, Takasaki J, Watanabe T, Fukunishi Y, Nakamura H, Orita M. |
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The in silico screening and X-ray structure analysis of the inhibitor complex of
Plasmodium falciparum orotidine 5'-monophosphate decarboxylase. Biochem. 2012 Aug;152(2):133-8. Takashima Y, Mizohata E, Krungkrai SR, Fukunishi Y, Kinoshita T, Sakata T, Matsumura H, Krungkrai J, Horii T, Inoue T. |
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LigandBox: A database for 3D structures of chemical compounds. BIOPHYSICS. 9, 113-121 (2013). T. Kawabata, Y. Sugihara, Y. Fukunishi, and H. Nakamura. |
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Improved estimation of protein-ligand binding free energy by using the ligand-entropy
and mobility of water molecules. Pharmaceuticals (Basel). 2013 Apr 26;6(5):604-22. doi: 10.3390/ph6050604. Fukunishi Y, Nakamura H. |
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非エバルト法に基づくGPUで加速されたG蛋白質共役型受容体の分子動力学計算 TSUBAME ESJ. 10, 8-12 (2013). 真下忠彰、河内隆行、福西快文、神谷成敏、高野優、福田育夫、中村春木 |
| 2012 |
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An accurate pharmacophore mapping method by NMR spectroscopy. Angew Chem Int Ed Engl. 51, 1362-5. Mizukoshi, Y., Abe, A., Takizawa, T., Hanzawa, H., Fukunishi, Y., Shimada, I. and Takahashi, H. |
| 2011 |
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Catalytic mechanism of the primary human prostaglandin F2a synthase, aldo-keto reductase 1B1 - prostaglandin D2synthase activity in the absence of NADP(H). FEBS journal. 278, 1288-1298. Nanae Nagata, Yukiko Kusakari, Yoshifumi Fukunishi, Tsuyoshi Inoue and Yoshihiro Urade. |
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Structure determination of a protein assembly by amino acid selective cross-saturation. Proteins. vol 79, 179-190. Eiji Kanamori, Shunsuke Igarashi, Masanori Osawa, Yoshifumi Fukunishi, Ichio Shimada, Haruki Nakamura. |
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Structure determination of a protein assembly by amino acid selective cross-saturation. Proteins. 79, 179-90. Kanamori, E., Igarashi, S., Osawa, M., Fukunishi, Y., Shimada, I. and Nakamura, H. |
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Prediction of ligand-binding sites of proteins by molecular docking calculation for a random ligand library. Protein Science. 20, 95-106. Yoshifumi Fukunishi, Haruki Nakamura |
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Prediction of positions of active compounds makes it possible to increase activity in fragment-based drug development. Pharmaceuticals. 4, 758-69. Fukunishi, Y. |
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Catalytic mechanism of the primary human prostaglandin F2alpha synthase, aldo-keto reductase 1B1--prostaglandin D2 synthase activity in the absence of NADP(H). FEBS J. 278, 1288-98. Nagata, N., Kusakari, Y., Fukunishi, Y., Inoue, T. and Urade, Y. |
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Rapid identification of protein-protein interfaces for the construction of a complex model based on multiple unassigned signals by using time-sharing NMR measurements. J Struct Biol. 174, 434-42. Kodama, Y., Reese, M. L., Shimba, N., Ono, K., Kanamori, E., Dotsch, V., Noguchi, S., Fukunishi, Y., Suzuki, E., Shimada, I. and Takahashi, H. |
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Definition of Drug-Likeness for Compound Affinity. J Chem Inf Model. 51, 1012-6. Fukunishi, Y. and Nakamura, H. |
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Cannabidiol-2',6'-dimethyl ether as an effective protector of 15-lipoxygenase-mediated low-density lipoprotein oxidation in vitro. Biol Pharm Bull. 34, 1252-6. Takeda, S., Hirayama, A., Urata, S., Mano, N., Fukagawa, K., Imamura, M., Irii, A., Kitajima, S., Masuyama, T., Nomiyama, M., Tatei, S., Tomita, S., Kudo, T., Noguchi, M., Yamaguchi, Y., Okamoto, Y., Amamoto, T., Fukunishi, Y., Watanabe, K., Omiecinski, C. J. and Aramaki, H. |
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Selection of in silico drug screening results for G-protein-coupled receptors by using universal active probes. J Chem Inf Model. 51, 2398-407. Wada, M., Kanamori, E., Nakamura, H. and Fukunishi, Y. |
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Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR. J Mol Graph Model. 31, 20-7. Fukunishi, Y., Mizukoshi, Y., Takeuchi, K., Shimada, I., Takahashi, H. and Nakamura, H. |
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Crystallization and preliminary X-ray diffraction analysis of mouse prostaglandin F2alpha synthase, AKR1B3. Acta Crystallogr Sect F Struct Biol Cryst Commun. 67, 1630-2. Takashima, Y., Hatanaka, S., Mizohata, E., Nagata, N., Fukunishi, Y., Matsumura, H., Urade, Y. and Inoue, T. |
| 2010 |
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Quantitative analysis of aggregation-solubility relationship by in-silico solubility prediction. International Journal of High Throughput Screening. 1, 99-107. Tadaaki Mashimo, Yoshifumi Fukunishi, Masaya Orita, Naoko Katayama, Shigeo Fujita, Haruki Nakamura |
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Structural ensemble in computational drug screening. Expert Opin. Drug Metab. Toxicol. vol 6, No 7, 1-15. Yoshifumi Fukunishi |
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Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction. CURRENT TOPICS IN MEDICINAL CHEMISTRY. vol 10, No 6, 680-694. Yoshifumi Fukunishi |
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Development of Chemical Compound Libraries for In Silico Drug Screening. Current Computer - Aided Drug Design. vol 6, No 2, June, 90-102. Yoshifumi Fukunishi, Lintuluoto Masami |
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Selection of in-silico drug screening result by using universal active probes (UAPs). Journal of Chemical Information and Modeling. 50, 1233-1240. Fukunishi, Yoshifumi; Ono, Kazuki; Orita, Masaya; Nakamura, Haruki |
| 2009 |
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Calculation of protein-ligand binding free energy using smooth reaction path generation (SRPG) method; comparing the explicit water model, GB/SA model and docking score function. Genome Informatics. 23, 58-97. D. Mitomo, Y. Fukunishi, J. Higo, H. Nakamura |
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A similarity search using molecular topological graphs. Journal of Biomedicine and Biotechnology. Article ID 231780. Y. Fukunishi, H. Nakamura |
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Protein-ligand binding free energy calculation by the smooth reaction path generation (SRPG) method. J. Chem. Inf. Model. 49, 1944-1951. Y. Fukunishi, D. Mitomo, H. Nakamura |
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Structure-based drug screening and ligand-based drug screening with machine learning. Combinatorial Chemistry and High Throughput Screening. vol 12, No. 4, 397-408. Y. Fukunishi |
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In silico fragment screening by replica generation (FSRG) method for fragment-based drug design. Journal of Chemical Information and Modeling. 49, 925-933. Y. Fukunishi, Tadaaki Mashimo, Masaya Orita, Kazuki Ohno, Haruki Nakamura |
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Advanced in-silico drug screeing to achieve high hit ratio-development of 3D-compound database. Synthesiology. 2, 60-68. Yoshifumi Fukunishi, Yuusuke Sugihara, Yoshiaki Mikami, Kohta Sakai, Hiroshi Kusudo, Haruki Nakamura |
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A new method for in-silico drug screening and similarity search using molecular-dynamics maximum-volume overlap (MD-MVO) method. Journal of Molecular Graphics and Modelling. 27, 628-636. Y. Fukunishi, H. Nakamura |
| 2008 |
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In silico prediction of chemical block of cardiac repolarization reserve K+ current. Journal of Physiological Science. 58, 459-470. Atsushi Inanobe, Narutoshi Kamiya, Shingo Murakami, Yoshifumi Fukunishi, Haruki Nakamura, Yoshihisa Kurachi |
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A method to enhance the hit ratio by a combination of structure-based drug screening and ligand-based screening”,Computational Biology and Chemistry. Advances and Applications. 1, 19-28. Katsumi Omagari, Daisuke Mitomo, Satoru Kubota, Haruki Nakamura, Yoshifumi Fukunishi |
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Improvement of protein-compound docking scores by using amino-acid sequence similarities of proteins. Journal of chemical information and modeling. 48, 148-156. Y. Fukunishi, H. Nakamura |
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Prediction of protein-ligand complex by docking software guided by other complex structures. Journal of Molecular Graphics and Modelling. 26, 1030-1033. Y. Fukunishi, H. Nakamura |
| 2007 |
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Docking of protein molecular surfaces with evolutionary trace analysis. Proteins. 69, 832-838. E. Kanamori, Y. Murakami, Y. Tsuchiya, D. M. Standley, H. Nakamura, K. Kinoshita |
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Structure-based Drug Screening and Ligand-Based Drug Screening Toward Protein-Compound Network. AIP conference proceeding. 963, 311-314. Dec 26, 2007, COMPUTATION IN MODERN SCIENCE AND ENGINEERING: Proceedings of the International Conference on Computational Methods in Science and Engineering 2007 (ICCMSE 2007): VOLUME 2, PARTS A and B; DOI:10.1063/1.2836070 Y. Fukunishi |
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Mutational Analysis of Block and Facilitation of HERG Current by A Class III Anti-Arrhythmic Agent, Nifekalant. CHANNELS. 1, 198-208. Yukio Hosaka, Miki Iwata, Narutoshi Kamiya, Mitsuhiko Yamada, Kengo Kinoshita, Yoshifumi Fukunishi, Kenji Tsujimae, Hiroshi Hibino, Yoshihusa Aizawa, Atsushi Inanobe, Haruki Nakamura, Yoshihisa Kurachi |
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In silico drug screening method based on the protein-compound affinity matrix using the factor selection technique. European Journal of Medicinal Chemistry. 42, 1-11. M. Sukumaran, S. Hojo, H. Tsujishita, H. Nakamura, Y. Fukunishi |
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Finding ligands for G-protein coupled receptors based on the protein-compound affinity matrix. Journal of Molecular Graphics and Modelling. 25, 633-43. Y. Fukunishi, S. Kubota, H. Nakamura |
| 2006 |
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An efficient in silico screening method based on the protein-compound affinity matrix and its application to the design of a focused library for cytochrome P450 (CYP) ligands. Journal of chemical information and modeling. 46, 2610-22. Y. Fukunishi, S. Hojo, H.Nakamura |
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Noise reduction method for molecular interaction energy: application to in silico drug screening and in silico target protein screening. Journal of Chemical Information and Modeling. 46, 2071-2084. Y. Fukunishi, S. Kubota, H. Nakamura |
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Classification of chemical compounds by protein-compound docking for use in designing a focused library. Journal of Medicinal Chemistry. 49, 523-533. Y. Fukunishi, Y. Mikami, K. Takedomi, M. Yamanouchi, H. Shima, H. Nakamura |
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Generation of a flexible loop structural ensemble and its application to induced-fit structural changes following ligand binding. BIOPHYSICS. 2, 1-12. Yukihisa S. Watanabe, Yoshifumi Fukunishi and Haruki Nakamura |
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Construction of an extended invariant for an arbitrary ordinary differential equation with its development in a numerical integration algorithm. Phys Rev E. 73, 026703. Ikuo Fukuda and Haruki Nakamura |
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A virtual active compound produced from the negative image of a ligand-binding pocket, and its application to in-silico drug screening. Journal of Computer-Aided Mol Design. 20, 237-48. Y. Fukunishi, S. Kubota, C. Kanai, H. Nakamura |
| 2005 |
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Similarity among receptor pockets and among compounds: Analysis and application to in silico ligand screening. Journal of Molecular Graphics and Modelling. 24, 34-45. Y. Fukunishi, Y. Mikami, H. Nakamura |
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Multiple target screening method for robust and accurate in silico screening. Journal of Molecular Graphics and Modelling. 25, 61-70. Y. Fukunishi, Y. Mikami, S. Kubota, H. Nakamura |
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Deterministic design for Tsallis distribution sampling. Chem. Phys. Lett. 405, 364-370. Ikuo Fukuda, Masaru Horie, and Haruki Nakamura |
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Molecular dynamics sampling scheme realizing multiple distributions. Phys Rev E. 71, 046708. Ikuo Fukuda, Masaru Horie, and Haruki Nakamura |
| 2004 |
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Stochastic formulation of sampling dynamics in generalized ensemble methods. Physical Review E. 69, 021101. Jae Gil Kim, Yoshifumi Fukunishi, Akinori Kidera and Haruki Nakamura |
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Efficiency in Generation of the Boltzmann-Gibbs Distribution by the Tsallis Dynamics Re-weighting Method. The Journal of Physical Chemistry B, in press. Ikuo Fukuda and Haruki Nakamura |
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Modelling of third cytoplasmic loop of bovine rhodopsin by multicanonical molecular dynamics. Journal of Molecular Graphics and Modelling. 23, 59-68. Yukihisa S. Watanabe, Yoshifumi Fukunishi and Haruki Nakamura |
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Average energy guided simulated tempering implemented into molecular dynamics algorithm for protein folding simulation. Chemical Physics Letters. 392, 34-39. Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura |
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Multicanonical molecular dynamics algorithm employing adaptive force-biased iteration scheme. Phys. Rev. E. 70, 057103. Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura |
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Free Energy Landscapes of Small Peptides in an Implicit Solvent Model Determined by Force-Biased Multicanonical Molecular Dynamics Simulation. Chemical Physics Letters. 400, 258-263. Yukihisa S. Watanabe, Jae Gil Kim, Yoshifumi Fukunishi and Haruki Nakamura |
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A hybrid method of molecular dynamics and harmonic dynamics for docking of flexible ligands to flexible receptors. Journal of Computational Chemistry. 25: 1995-2005. Rie Tatsumi, Yoshifumi Fukunishi, and Haruki Nakamura |
| 2003 |
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Dynamical origin of uniform sampling in multicanonical ensemble. Physical Review E. 67, 11105. Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura |
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Determination of multicanonical weight based on a stochastic model of sampling dynamics. Physical Review E. 68, 021110. Jae Gil Kim, Yoshifumi Fukunishi, Akinori Kidera and Haruki Nakamura |
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The filling potential method: A method for estimating the free energy surface for protein-ligand docking. J. Phys. Chem. B. 107, 13201-13210. Yoshifumi Fukunishi, Yoshiaki Mikami, and Haruki Nakamura |
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Deterministic generation of the Boltzmann-Gibbs distribution and the free energy calculation from the Tsallis distribution. Chemical Physics Letters. 382, 367-373. Ikuo Fukuda and Haruki Nakamura |
| 2002 |
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Tsallis dynamics using the Nose-Hoover approach. Physical Review E. 65, 026105. Ikuo Fukuda and Haruki Nakamura |