3D分子設計チーム

研究詳細 : 重点課題

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。

myPrestロゴ

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/

myPrestイメージ

 

最近の主な成果

高効率薬物スクリーニング計算システムの開発

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
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.

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.

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
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

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.

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

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.

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.

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
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
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.

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.

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.

LigandBox: A database for 3D structures of chemical compounds.
BIOPHYSICS. 9, 113-121 (2013).
T. Kawabata, Y. Sugihara, Y. Fukunishi, and H. Nakamura.

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.

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
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
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.

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.

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.

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

Prediction of positions of active compounds makes it possible to increase activity in fragment-based drug development.
Pharmaceuticals. 4, 758-69.
Fukunishi, Y.

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.

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.

Definition of Drug-Likeness for Compound Affinity.
J Chem Inf Model. 51, 1012-6.
Fukunishi, Y. and Nakamura, H.

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.

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.

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.

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
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

Structural ensemble in computational drug screening.
Expert Opin. Drug Metab. Toxicol. vol 6, No 7, 1-15.
Yoshifumi Fukunishi

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

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

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
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

A similarity search using molecular topological graphs.
Journal of Biomedicine and Biotechnology. Article ID 231780.
Y. Fukunishi, H. Nakamura

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

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

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

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

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
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

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

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

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
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

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

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

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

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
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

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

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

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

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

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
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

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

Deterministic design for Tsallis distribution sampling.
Chem. Phys. Lett. 405, 364-370.
Ikuo Fukuda, Masaru Horie, and Haruki Nakamura

Molecular dynamics sampling scheme realizing multiple distributions.
Phys Rev E. 71, 046708.
Ikuo Fukuda, Masaru Horie, and Haruki Nakamura

2004
Stochastic formulation of sampling dynamics in generalized ensemble methods.
Physical Review E. 69, 021101.
Jae Gil Kim, Yoshifumi Fukunishi, Akinori Kidera and Haruki Nakamura

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

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

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

Multicanonical molecular dynamics algorithm employing adaptive force-biased iteration scheme.
Phys. Rev. E. 70, 057103.
Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura

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

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
Dynamical origin of uniform sampling in multicanonical ensemble.
Physical Review E. 67, 11105.
Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura

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

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

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
Tsallis dynamics using the Nose-Hoover approach.
Physical Review E. 65, 026105.
Ikuo Fukuda and Haruki Nakamura

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