第四室                                                                    

第四室は,当部の研究目標である医薬品の適正使用推進のための研究を,情報科学の観点から担当しています.

 

業務内容

 第四室は,医薬品の副作用発現に関するメカニズムを,データベースや量子化学などの情報科学的手法を用いて解析する方法を開発することを目的の一つとしています.第四室はデータベースや分子シミュレーションのように,計算機を用いた解析に特徴があります.また第四室は,所内の研究情報ネットワークシステムの管理・監督を担当しています.

 

主な研究課題

1.      フラグメント分子軌道(FMO)法を用いた、医薬品の作用機序解析のための分子シミュレーション手法に関する研究

2.      有機化学部との共同研究による医薬品名称情報の収集及び調査研究、及び日本薬局方名称データベース(JP DB)及び日本医薬品一般的名称データベース(JAN DB)の開発

3.      研究情報ネットワークシステム(NIHS-NET)の管理・運用

 

スタッフ

室 長 中野達也 (なかの たつや,Nakano, Tatsuya

主任研究官 瀬川勝智 (せがわ かつのり,Segawa, Katsunori

研究助手 沖山佳生 (おきやま よしお,Okiyama, Yoshio

 

1.    フラグメント分子軌道(FMO)法を用いた、医薬品の作用機序解析のための分子シミュレーション手法に関する研究

 

フラグメント分子軌道法 参考文献

1)     Fedorov, D. G., Kitaura, K.: Modern methods for theoretical physical chemistry of biopolymers, Starikov, E. B., Lewis, J. P., Tanaka, S., Eds., Elsevier (2006) pp. 3-38.

2)     Nakano, T., Mochizuki, Y., Fukuzawa, K., Amari, S., Tanaka, S.: Modern methods for theoretical physical chemistry of biopolymers, Starikov, E. B., Lewis, J. P., Tanaka, S., Eds., Elsevier (2006) pp. 39-52.

3)     Fedorov, D. G., Kitaura, K.: J. Phys. Chem. A 111, 6904-6914 (2007)

4)     中野達也, 望月祐志, 甘利真司,小林将人,福澤薫,田中成典: J. Comput. Chem. Jpn. 6, 173-184 (2007)

5)     福澤薫, 中野達也, 加藤昭史, 望月祐志, 田中成典: J. Comput. Chem. Jpn. 6, 185-198 (2007)

6)     佐藤文俊, 中野達也, 望月祐志 編著: 生体分子量子化学計算, 森北出版, 東京, 2008.

7)     Fedorov, D. G., Kitaura, K., Eds.: The Fragment Molecular Orbital Method: Practical Applications to Large Molecular Systems, CRC Press, Boca Raton, 2009.

 

2.    有機化学部との共同研究による医薬品名称情報の収集及び調査研究、及び日本薬局方名称データベース(JP DB)及び日本医薬品一般的名称データベース(JAN DB)の開発

                        

日本薬局方名称データベース(JP DB)のホームページ           日本医薬品一般的名称データベース(JAN DB)のホームページ

 

3.    研究情報ネットワークシステム(NIHS-NET)の管理・運用

1Nakata, K., Nakano, T. and Kaminuma, T.: Bull. Natl. Inst. Health Sci., 114, 53-611996

2Nakata, K., Nakano, T., Takai, T. and Kaminuma, T.: Bull. Natl. Inst. Health Sci., 116, 92-1001998

3Nakata, K., Nakano, T., Takai, T., Komine, K. and Kaminuma, T.: Bull. Natl. Inst. Health Sci., 118, 107-116 2000

4Segawa, K., Nakano, T., Hayashi, Y. and Nakata, K.: Bull. Natl. Inst. Health Sci., 122, 34-362004

5)  Segawa, K., Nakano, T., Saito, Y.: Bull. Natl. Inst. Health Sci., 130, 75-772012

 

研究業績

[2010]

K. Yamagishi, K. Yamamoto, Y. Mochizuki, T. Nakano, S. Yamada, H. Tokiwa, "Flexible ligand recognition of peroxisome proliferator-activated receptor-g (PPARg)", Bioorg. Med. Chem. Lett. 20, 3344 (2010).

Y. Okiyama, T. Nakano, K. Yamashita, Y. Mochizuki, N. Taguchi, S. Tanaka, "Acceleration of fragment molecular orbital calculations with Cholesky decomposition approach", Chem. Phys. Lett. 490, 84-89 (2010).

Y. Mochizuki, K. Yamashita, K. Fukuzawa, K. Takematsu, H. Watanabe, N. Taguchi, Y. Okiyama, M. Tsuboi, T. Nakano, S. Tanaka, "Large-scale FMO-MP3 calculations on the surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA)", Chem. Phys. Lett. 493, 346-352 (2010)

H. Watanabe, Y. Okiyama, T. Nakano, S. Tanaka, Incorporation of solvation effects into the fragment molecular orbital calculations with the PoissonBoltzmann equation, Chem. Phys. Lett. 500, 116-119 (2010).

I. Kurisaki, K. Fukuzawa, T. Nakano, Y. Mochizuki, H. Watanabe, S. Tanaka, Fragment molecular orbital (FMO) study on stabilization mechanism of neuro-oncological ventral antigen (NOVA)RNA complex system, J. Mol. Struct. (THEOCHEM) 962, 45-55 (2010).

M. Sato, H. Yamataka, Y. Komeiji, Y. Mochizuki, T. Nakano, Does Amination of Formaldehyde Proceed Through a Zwitterionic Intermediate in Water? Fragment Molecular Orbital Molecular Dynamics Simulations by Using Constraint Dynamics, Chemistry A European Journal, 16, 6430-6433 (2010).

T. Ogawa, T. Nakano, The Extended Universal Force Field (XUFF): Theory and Applications, Chem-Bio. Info. J. 10, 111-133 (2010).

[2009]

Y. Komeiji, T. Ishikawa, Y. Mochizuki, H. Yamataka, T. Nakano, Fragment Molecular Orbital method-based Molecular Dynamics (FMO-MD) as a simulator for chemical reactions in explicit solvation, J. Comput. Chem. 30, 40-50 (2009).

Y. Komeiji, Y. Mochizuki, T. Nakano, and D. G. Fedorov, Fragment Molecular Orbital-based Molecular Dynamics (FMO-MD), a quantum simulation tool for large molecular systems, J. Mol. Struct. (Theochem), 898, 2-7 (2009).

T. Fujita, K. Fukuzawa, Y. Mochizuki, T. Nakano, S. Tanaka, "Accuracy of fragmentation in ab initio calculations of hydrated sodium cation", Chem. Phys. Lett. 478 295-300 (2009).

T. Watanabe, Y. Inadomi, H. Umeda, K. Fukuzawa, S. Tanaka, T. Nakano, U. Nagashima, "Fragment Molecular Orbital (FMO) and FMO-MO Calculations of DNA: Accuracy Validation of Energy and Interfragment Interaction Energy", J. Comp. Theor. Nanosci. 6, 1328-1337 (2009).

K. Takematsu, K. Fukuzawa, K. Omagari, S. Nakajima, K. Nakajima, Y. Mochizuki, T. Nakano, H. Watanabe, S. Tanaka, "Possibility of mutation prediction of influenza hemagglutinin by combination of hemadsorption experiment and quantum chemical calculation for antibody binding", J. Phys. Chem. B 113, 4991-4994 (2009).

N. Taguchi, Y. Mochizuki, T. Nakano, S. Amari, K. Fukuzawa, T. Ishikawa, M. Sakurai, S. Tanaka, "Fragment Molecular Orbital Calculations on Red Fluorescent Proteins (DsRed and mFruits)", J. Phys. Chem. B 113, 1153-1161 (2009).

Y. Okiyama, H. Watanabe, K. Fukuzawa, T. Nakano, Y. Mochizuki, T. Ishikawa, K. Ebina, S. Tanaka, "Application of the fragment molecular orbital method for determination of atomic charges on polypeptides. II. Towards an improvement of force fields used for classical molecular dynamics simulations", Chem. Phys. Lett. 467, 417-423 (2009).

T. Nakano, Y. Mochizuki, A. Kato, K. Fukuzawa, T. Ishikawa, S. Amari, I. Kurisaki, S. Tanaka, "Developments of FMO Methodology and Graphical User Interface in ABINIT-MP", in The Fragment Molecular Orbital Method: Practical Applications to Large Molecular Systems, D. G. Fedorov, K. Kitaura, Eds.; pp.37-62, CRC Press, Boca Raton, FL, 2009.

Y. Mochizuki, T. Nakano, N. Taguchi, S. Tanaka, "Excited States of Photoactive Proteins by Configuration Interaction Studies", in The Fragment Molecular Orbital Method: Practical Applications to Large Molecular Systems, D. G. Fedorov, K. Kitaura, Eds.; pp. 63-90, CRC Press, Boca Raton, FL, 2009.

K. Fukuzawa, Y. Mochizuki, T. Nakano, S. Tanaka, "Application of FMO Method to Specific Molecular Recognition of Biomacromolecules", in The Fragment Molecular Orbital Method: Practical Applications to Large Molecular Systems, D. G. Fedorov, K. Kitaura, Eds.; pp. 133-170, CRC Press, Boca Raton, FL, 2009.

[2008]

M. Ito, K. Fukuzawa, Y. Mochizuki, T. Nakano, S. Tanaka, Ab Initio Fragment Molecular Orbital Study of Molecular Interactions between Liganded Retinoid X Receptor and Its Coactivator; Part II: Influence of Mutations in Transcriptional Activation Function 2 Activating Domain Core on the Molecular Interactions, J. Phys. Chem. A 112, 1986-1998 (2008).

M. Sato, H. Yamataka, Y. Komeiji, Y. Mochizuki, T. Ishikawa, T. Nakano, How Does an SN2 Reaction Take Place in Solution? Full Ab Initio MD Simulations for the Hydrolysis of the Methyl Diazonium Ion, J. Am. Chem. Soc. 130, 2396-2397 (2008).

K. Koyano and T. Nakano, Interaction of HIV-1 aspartic protease with its inhibitor, by molecular dynamics and ab initio fragment molecular orbital method, J. Synchrotron Rad. 15, 239242 (2008).

Y. Mochizuki, K. Yamashita, T. Murase, T. Nakano, K. Fukuzawa, K. Takematsu, H. Watanabe, S. Tanaka, Large scale FMO-MP2 calculations on a massively parallel-vector computer, Chem. Phys. Lett. 457,  396-403 (2008).

T. Harada, K. Yamagishi, T. Nakano, K. Kitaura, H. Tokiwa, "Ab initio fragment molecular orbital study of ligand binding to human progesterone receptor ligand-binding domain", Naunyn-Schmiedeberg's Arch. Pharmac. 377, 607-615 (2008).

M. Ito, K. Fukuzawa, T. Ishikawa, Y. Mochizuki, T. Nakano, and S. Tanaka, Ab Initio Fragment Molecular Orbital Study of Molecular Interactions in Liganded Retinoid X Receptor: Specification of Residues Associated with Ligand Inducible Information Transmission, J. Phys. Chem. B, 112, 12081-12094 (2008).

T. Ishikawa, Y. Mochizuki, S. Amari, T. Nakano, S. Tanaka, K. Tanaka, An application of fragment interaction analysis based on local MP2, Chem. Phys. Lett. 463, 189-194 (2008).

[2007]

Y. Komeiji, T. Ishikawa, Y. Mochizuki, H. Yamataka, T. Nakano, In "Computation in Modern Science and Engineering - Proc. ICCMSE2007 (T. E. Simos and G. Maroulis, eds, AIP), pp. 1261-1264 (2007).

Y. Okiyama, H. Watanabe, K. Fukuzawa, T. Nakano, Y. Mochizuki, T. Ishikawa, S. Tanaka, K. Ebina, Application of the fragment molecular orbital method for determination of atomic charges on polypeptides, Chem. Phys. Lett. 449, 329-335 (2007).

Y. Mochizuki, K. Tanaka, K. Yamashita, T. Ishikawa, T. Nakano, S. Amari, K. Segawa, T. Murase, H. Tokiwa, M. Sakurai, Parallelized integral-direct CIS(D) calculations with multilayer fragment molecular orbital scheme, Theor. Chem. Acc. 117, 541-553 (2007).

Y. Mochizuki, T. Nakano, S. Amari, T. Ishikawa, K. Tanaka, M. Sakurai and S. Tanaka, Fragment molecular orbital calculations on red fluorescent protein (DsRed), Chem. Phys. Lett. 433, 360-367 (2007).

Y. Mochizuki, Y. Komeiji, T. Ishikawa, T. Nakano, H. Yamataka, A fully quantum mechanical simulation study on the lowest np* state of hydrated formaldehyde, Chem. Phys. Lett. 437, 66-72 (2007).

M. Ito, K. Fukuzawa, Y. Mochizuki, T. Nakano, and S. Tanaka, Ab Initio Fragment Molecular Orbital Study of Molecular Interactions between Liganded Retinoid X Receptor and Its Coactivator: Roles of Helix 12 in the Coactivator Binding Mechanism, J. Phys. Chem. B 111, 3525-3533 (2007).

I. Kurisaki, K. Fukuzawa, Y. Komeiji, Y. Mochizuki, T. Nakano, J. Imada, A. Chmielewski, S. M. Rothstein, H. Watanabe, and S. Tanaka, Visualization analysis of Inter-fragment interaction energies of CRP-cAMP-DNA complex based on the fragment molecular orbital method, Biophys. Chem. 130, 1-9 (2007).

T. Ishikawa, Y. Mochizuki, S. Amari, T. Nakano, H. Tokiwa, S. Tanaka and K. Tanaka, Fragment interaction analysis based on local MP2, Theor. Chem. Acc. 118, 937945 (2007).

T. Watanabe, Y. Inadomi, K. Fukuzawa, T. Nakano, S. Tanaka, L. Nilsson, U. Nagashima, DNA and Estrogen Receptor Interaction Revealed by Fragment Molecular Orbital Calculations, J. Phys. Chem. B 111, 9621-9627 (2007).