2024/04/20 更新

写真a

ハヤシ トモヒコ
林 智彦
HAYASHI Tomohiko
所属
教育研究院 自然科学系 情報電子工学系列 准教授
工学部 工学科 准教授
自然科学研究科 電気情報工学専攻 准教授
職名
准教授
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外部リンク

学位

  • 博士(工学) ( 2012年9月   東京工業大学 )

研究キーワード

  • 溶液論

  • 生物物理学

  • 形態計測学的アプローチ

  • 積分方程式理論

  • 計算科学

研究分野

  • 自然科学一般 / 生物物理、化学物理、ソフトマターの物理

経歴(researchmap)

  • 新潟大学   工学部 工学科   准教授

    2023年4月 - 現在

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    国名:日本国

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  • 京都大学   エネルギー理工学研究所   協力研究員

    2019年10月 - 現在

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  • 新潟大学   工学部 工学科   助教

    2019年10月 - 2023年3月

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  • 立命館大学   薬学部   講師

    2019年4月 - 2020年3月

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  • 京都大学   エネルギー理工学研究所   研究員

    2013年4月 - 2019年9月

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  • 東京工業大学   バイオ研究基盤支援総合センター   研究員

    2012年10月 - 2013年3月

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▶ 全件表示

経歴

  • 新潟大学   自然科学研究科 電気情報工学専攻   准教授

    2023年4月 - 現在

  • 新潟大学   工学部 工学科   准教授

    2023年4月 - 現在

  • 新潟大学   教育研究院 自然科学系 情報電子工学系列   准教授

    2023年4月 - 現在

  • 新潟大学   工学部 工学科   助教

    2019年10月 - 2023年3月

学歴

  • 東京工業大学   生命理工学研究科   生体分子機能工学専攻

    - 2012年9月

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    国名: 日本国

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  • 東京工業大学   生命理工学部   生命工学科

    - 2005年9月

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    国名: 日本国

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所属学協会

  • 日本生物物理学会

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  • 米国生物物理学会(Biophysical Society, U.S.A.)

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  • 日本臨床バイオメカニクス学会

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  • 日本化学会

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論文

  • Nonadditivities of the Particle Sizes Hidden in Model Pair Potentials and Their Effects on Physical Adsorptions

    Ken-ichi Amano, Satoshi Furukawa, Yuto Kubo, Yuka Nakamura, Rina Ishii, Ayane Tanase, Masahiro Maebayashi, Tomohiko Hayashi, Naoya Nishi, Tetsuo Sakka

    Langmuir   39 ( 37 )   12999 - 13007   2023年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/acs.langmuir.3c00968

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  • Physical pictures of rotation mechanisms of F1- and V1-ATPases: Leading roles of translational, configurational entropy of water

    Satoshi Yasuda, Tomohiko Hayashi, Takeshi Murata, Masahiro Kinoshita

    Frontiers in Molecular Biosciences   10   2023年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    We aim to develop a theory based on a concept other than the chemo-mechanical coupling (transduction of chemical free energy of ATP to mechanical work) for an ATP-driven protein complex. Experimental results conflicting with the chemo-mechanical coupling have recently emerged. We claim that the system comprises not only the protein complex but also the aqueous solution in which the protein complex is immersed and the system performs essentially no mechanical work. We perform statistical-mechanical analyses on V<sub>1</sub>-ATPase (the A<sub>3</sub>B<sub>3</sub>DF complex) for which crystal structures in more different states are experimentally known than for F<sub>1</sub>-ATPase (the α<sub>3</sub>β<sub>3</sub>γ complex). Molecular and atomistic models are employed for water and the structure of V<sub>1</sub>-ATPase, respectively. The entropy originating from the translational displacement of water molecules in the system is treated as a pivotal factor. We find that the packing structure of the catalytic dwell state of V<sub>1</sub>-ATPase is constructed by the interplay of ATP bindings to two of the A subunits and incorporation of the DF subunit. The packing structure represents the nonuniformity with respect to the closeness of packing of the atoms in constituent proteins and protein interfaces. The physical picture of rotation mechanism of F<sub>1</sub>-ATPase recently constructed by Kinoshita is examined, and common points and differences between F<sub>1</sub>- and V<sub>1</sub>-ATPases are revealed. An ATP hydrolysis cycle comprises binding of ATP to the protein complex, hydrolysis of ATP into ADP and Pi in it, and dissociation of ADP and Pi from it. During each cycle, the chemical compounds bound to the three A or β subunits and the packing structure of the A<sub>3</sub>B<sub>3</sub> or α<sub>3</sub>β<sub>3</sub> complex are sequentially changed, which induces the unidirectional rotation of the central shaft for retaining the packing structure of the A<sub>3</sub>B<sub>3</sub>DF or α<sub>3</sub>β<sub>3</sub>γ complex stabilized for almost maximizing the water entropy. The torque driving the rotation is generated by water with no input of chemical free energy. The presence of ATP is indispensable as a trigger of the torque generation. The ATP hydrolysis or synthesis reaction is tightly coupled to the rotation of the central shaft in the normal or inverse direction through the water-entropy effect.

    DOI: 10.3389/fmolb.2023.1159603

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  • 円板状半月板を有する若年小児の大腿骨外側顆部の3次元形状評価 査読

    青木 一磨, 林 智彦, 渡邉 聡, 林 豊彦, 古賀 良生, 大森 豪, 小林 公一, 坂本 信

    臨床バイオメカニクス   43   97 - 105   2022年10月

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  • A methodology for creating mutants of G‐protein coupled receptors stabilized in active state by combining statistical thermodynamics and evolutionary molecular engineering 査読

    Taisei Yamamoto, Satoshi Yasuda, Rinshi S. Kasai, Ryosuke Nakano, Simon Hikiri, Kanna Sugaya, Tomohiko Hayashi, Satoshi Ogasawara, Mitsunori Shiroishi, Takahiro K. Fujiwara, Masahiro Kinoshita, Takeshi Murata

    Protein Science   31 ( 10 )   2022年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/pro.4425

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pro.4425

  • A methodology for creating thermostabilized mutants of G‐protein coupled receptors by combining statistical thermodynamics and evolutionary molecular engineering 査読

    Kanna Sugaya, Satoshi Yasuda, Shingo Sato, Chen Sisi, Taisei Yamamoto, Daisuke Umeno, Tomoaki Matsuura, Tomohiko Hayashi, Satoshi Ogasawara, Masahiro Kinoshita, Takeshi Murata

    Protein Science   31 ( 9 )   2022年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    DOI: 10.1002/pro.4404

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pro.4404

  • Development of an Outward Proton Pumping Rhodopsin with a New Record in Thermostability by Means of Amino Acid Mutations 査読 国際誌

    Satoshi Yasuda, Tomoki Akiyama, Keiichi Kojima, Tetsuya Ueta, Tomohiko Hayashi, Satoshi Ogasawara, Satoru Nagatoishi, Kouhei Tsumoto, Naoki Kunishima, Yuki Sudo, Masahiro Kinoshita, Takeshi Murata

    The Journal of Physical Chemistry B   126 ( 5 )   1004 - 1015   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    We have developed a methodology for identifying further thermostabilizing mutations for an intrinsically thermostable membrane protein. The methodology comprises the following steps: (1) identifying thermostabilizing single mutations (TSSMs) for residues in the transmembrane region using our physics-based method; (2) identifying TSSMs for residues in the extracellular and intracellular regions, which are in aqueous environment, using an empirical force field FoldX; and (3) combining the TSSMs identified in steps (1) and (2) to construct multiple mutations. The methodology is illustrated for thermophilic rhodopsin whose apparent midpoint temperature of thermal denaturation Tm is ∼91.8 °C. The TSSMs previously identified in step (1) were F90K, F90R, and Y91I with ΔTm ∼5.6, ∼5.5, and ∼2.9 °C, respectively, and those in step (2) were V79K, T114D, A115P, and A116E with ΔTm ∼2.7, ∼4.2, ∼2.6, and ∼2.3 °C, respectively (ΔTm denotes the increase in Tm). In this study, we construct triple and quadruple mutants, F90K+Y91I+T114D and F90K+Y91I+V79K+T114D. The values of ΔTm for these multiple mutants are ∼11.4 and ∼13.5 °C, respectively. Tm of the quadruple mutant (∼105.3 °C) establishes a new record in a class of outward proton pumping rhodopsins. It is higher than Tm of Rubrobacter xylanophilus rhodopsin (∼100.8 °C) that was the most thermostable in the class before this study.

    DOI: 10.1021/acs.jpcb.1c08684

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  • Controlling the Rigidity of Kinesin-Propelled Microtubules in an <i>In Vitro</i> Gliding Assay Using the Deep-Sea Osmolyte Trimethylamine <i>N</i>-Oxide 査読 国際誌

    Arif Md. Rashedul Kabir, Tasrina Munmun, Tomohiko Hayashi, Satoshi Yasuda, Atsushi P. Kimura, Masahiro Kinoshita, Takeshi Murata, Kazuki Sada, Akira Kakugo

    ACS Omega   7 ( 4 )   3796 - 3803   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/acsomega.1c06699

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  • Comparison based on statistical thermodynamics between globule-to-coil transition of poly(N-isopropylacrylamide) and cold denaturation of a protein 査読 国際誌

    Masao Inoue, Tomohiko Hayashi, Simon Hikiri, Mitsunori Ikeguchi, Masahiro Kinoshita

    Journal of Molecular Liquids   317   114129   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.molliq.2020.114129

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  • Development and structural determination of an anti-prpc aptamer that blocks pathological conformational conversion of prion protein 査読 国際誌

    Tsukasa Mashima, Joon-Hwa Lee, Yuji O. Kamatari, Tomohiko Hayashi, Takashi Nagata, Fumiko Nishikawa, Satoshi Nishikawa, Masahiro Kinoshita, Kazuo Kuwata, Masato Katahira

    Scientific Reports   10   4934   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-020-61966-4

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  • Methodology for Further Thermostabilization of an Intrinsically Thermostable Membrane Protein Using Amino Acid Mutations with Its Original Function Being Retained 査読 国際誌

    Satoshi Yasuda, Tomoki Akiyama, Sayaka Nemoto, Tomohiko Hayashi, Tetsuya Ueta, Keiichi Kojima, Takashi Tsukamoto, Satoru Nagatoishi, Kouhei Tsumoto, Yuki Sudo, Masahiro Kinoshita, Takeshi Murata

    Journal of Chemical Information and Modeling   60 ( 3 )   1709 - 1716   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.jcim.0c00063

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  • Hydration properties of a protein at low and high pressures: Physics of pressure denaturation 査読 国際誌

    Masao Inoue, Tomohiko Hayashi, Simon Hikiri, Mitsunori Ikeguchi, Masahiro Kinoshita

    The Journal of Chemical Physics   152   065103   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.5140499

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  • How Does a Microbial Rhodopsin RxR Realize Its Exceptionally High Thermostability with the Proton-Pumping Function Being Retained? 査読 国際誌

    Tomohiko Hayashi, Satoshi Yasuda, Kano Suzuki, Tomoki Akiyama, Kanae Kanehara, Keiichi Kojima, Mikio Tanabe, Ryuichi Kato, Toshiya Senda, Yuki Sudo, Takeshi Murata, Masahiro Kinoshita

    The Journal of Physical Chemistry B   124 ( 6 )   990 - 1000   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    We often encounter a case where two proteins, whose amino-acid sequences are similar, are quite different with regard to the thermostability. As a striking example, we consider the two seven-transmembrane proteins: recently discovered Rubrobacter xylanophilus rhodopsin (RxR) and long-known bacteriorhodopsin from Halobacterium salinarum (HsBR). They commonly function as a light-driven proton pump across the membrane. Though their sequence similarity and identity are ∼71 and ∼45%, respectively, RxR is much more thermostable than HsBR. In this study, we solve the three-dimensional structure of RxR using X-ray crystallography and find that the backbone structures of RxR and HsBR are surprisingly similar to each other: The root-mean-square deviation for the two structures calculated using the backbone Cα atoms of the seven helices is only 0.86 Å, which makes the large stability difference more puzzling. We calculate the thermostability measure and its energetic and entropic components for RxR and HsBR using our recently developed statistical-mechanical theory. The same type of calculation is independently performed for the portions playing essential roles in the proton-pumping function, helices 3 and 7, and their structural properties are related to the probable roles of water molecules in the proton-transporting mechanism. We succeed in elucidating how RxR realizes its exceptionally high stability with the original function being retained. This study provides an important first step toward the establishment of a method correlating microscopic, geometric characteristics of a protein with its thermodynamic properties and enhancing the thermostability through amino-acid mutations without vitiating the original function.

    DOI: 10.1021/acs.jpcb.9b10700

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  • Mechanism of globule-to-coil transition of poly(<i>N</i>-isopropylacrylamide) in water: Relevance to cold denaturation of a protein 査読 国際誌

    Masao Inoue, Tomohiko Hayashi, Simon Hikiri, Mitsunori Ikeguchi, Masahiro Kinoshita

    Journal of Molecular Liquids   292   111374   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.molliq.2019.111374

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  • How Does the Recently Discovered Peptide MIP Exhibit Much Higher Binding Affinity than an Anticancer Protein p53 for an Oncoprotein MDM2? 査読 国際誌

    Tatsuya Yamada, Tomohiko Hayashi, Simon Hikiri, Naohiro Kobayashi, Hiroshi Yanagawa, Mitsunori Ikeguchi, Masato Katahira, Takashi Nagata, Masahiro Kinoshita

    Journal of Chemical Information and Modeling   59   3533 - 3544   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.jcim.9b00226

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  • An accurate and rapid method for calculating hydration free energies of a variety of solutes including proteins 査読 国際誌

    Simon Hikiri, Tomohiko Hayashi, Masao Inoue, Toru Ekimoto, Mitsunori Ikeguchi, Masahiro Kinoshita

    The Journal of Chemical Physics   150 ( 17 )   175101 - 175101   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.5093110

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  • Analyses based on statistical thermodynamics for large difference between thermophilic rhodopsin and xanthorhodopsin in terms of thermostability 査読 国際誌

    Satoshi Yasuda, Tomohiko Hayashi, Yuta Kajiwara, Takeshi Murata, Masahiro Kinoshita

    The Journal of Chemical Physics   150 ( 5 )   055101 - 055101   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.5082217

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  • Statistical thermodynamics for the unexpectedly large difference between disaccharide stereoisomers in terms of solubility in water 査読 国際誌

    Simon Hikiri, Tomohiko Hayashi, Mitsunori Ikeguchi, Masahiro Kinoshita

    Physical Chemistry Chemical Physics   20   23684 - 23693   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c8cp04377a

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  • Universal effects of solvent species on the stabilized structure of a protein 査読 国際共著 国際誌

    Tomohiko Hayashi, Masao Inoue, Satoshi Yasuda, Emanuele Petretto, Tatjana Škrbić, Achille Giacometti, Masahiro Kinoshita

    The Journal of Chemical Physics   149   045105   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.5042111

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  • Physical Origin of Thermostabilization by a Quadruple Mutation for the Adenosine A<sub>2a</sub> Receptor in the Active State 査読 国際誌

    Yuta Kajiwara, Satoshi Yasuda, Simon Hikiri, Tomohiko Hayashi, Mitsunori Ikeguchi, Takeshi Murata, Masahiro Kinoshita

    The Journal of Physical Chemistry B   122   4418 - 4427   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.jpcb.8b00443

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  • Mechanism of protein–RNA recognition: analysis based on the statistical mechanics of hydration 査読 国際誌

    Tomohiko Hayashi, Tomoaki Matsuda, Takashi Nagata, Masato Katahira, Masahiro Kinoshita

    Physical Chemistry Chemical Physics   20   9167 - 9180   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c8cp00155c

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  • Potential of mean force between spherical particles in an ionic liquid and its decomposition into energetic and entropic components: An analysis using an integral equation theory 査読 国際誌

    Ken-ichi Amano, Tomohiko Hayashi, Kota Hashimoto, Naoya Nishi, Tetsuo Sakka

    Journal of Molecular Liquids   257   121 - 131   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.molliq.2018.02.089

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  • Entropic enrichment of cosolvent near a very large solute immersed in solvent-cosolvent binary mixture: Anomalous dependence on bulk cosolvent concentration 査読 国際誌

    Masahiro Kinoshita, Tomohiko Hayashi

    Journal of Molecular Liquids   247   403 - 410   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.molliq.2017.09.108

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  • Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail 査読 国際共著 国際誌

    Tomohiko Hayashi, Satoshi Yasuda, Tatjana Škrbić, Achille Giacometti, Masahiro Kinoshita

    The Journal of Chemical Physics   147   125102   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.4999376

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  • Unified elucidation of the entropy-driven and -opposed hydrophobic effects 査読 国際誌

    Masahiro Kinoshita, Tomohiko Hayashi

    Physical Chemistry Chemical Physics   19   25891 - 25904   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c7cp05160c

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  • Effects of salt or cosolvent addition on solubility of a hydrophobic solute in water: Relevance to those on thermal stability of a protein 査読 国際誌

    Shota Murakami, Tomohiko Hayashi, Masahiro Kinoshita

    The Journal of Chemical Physics   146   055102   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1063/1.4975165

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  • Statistical thermodynamics of aromatic–aromatic interactions in aqueous solution 査読 国際誌

    Tomohiko Hayashi, Masahiro Kinoshita

    Physical Chemistry Chemical Physics   18   32406 - 32417   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c6cp06000e

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  • Water based on a molecular model behaves like a hard-sphere solvent for a nonpolar solute when the reference interaction site model and related theories are employed 査読 国際誌

    Tomohiko Hayashi, Hiraku Oshima, Yuichi Harano, Masahiro Kinoshita

    Journal of Physics: Condensed Matter   28   344033   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1088/0953-8984/28/34/344003

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  • Statistical Thermodynamics for Actin-Myosin Binding: The Crucial Importance of Hydration Effects 査読 国際誌

    Hiraku Oshima, Tomohiko Hayashi, Masahiro Kinoshita

    Biophysical Journal   110   2496 - 2506   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bpj.2016.05.006

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  • On the physics of thermal-stability changes upon mutations of a protein 査読 国際誌

    Shota Murakami, Hiraku Oshima, Tomohiko Hayashi, Masahiro Kinoshita

    The Journal of Chemical Physics   143 ( 12 )   215102   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AIP Publishing  

    It is of great interest from both scientific and practical viewpoints to theoretically predict the thermal-stability changes upon mutations of a protein. However, such a prediction is an intricate task. Up to now, significantly many approaches for the prediction have been reported in the literature. They always include parameters which are adjusted so that the prediction results can be best fitted to the experimental data for a sufficiently large set of proteins and mutations. The inclusion is necessitated to achieve satisfactorily high prediction performance. A problem is that the resulting values of the parameters are often physically meaningless, and the physicochemical factors governing the thermal-stability changes upon mutations are rather ambiguous. Here, we develop a new measure of the thermal stability. Protein folding is accompanied by a large gain of water entropy (the entropic excluded-volume (EV) effect), loss of protein conformational entropy, and increase in enthalpy. The enthalpy increase originates primarily from the following: The energy increase due to the break of protein-water hydrogen bonds (HBs) upon folding cannot completely be cancelled out by the energy decrease brought by the formation of protein intramolecular HBs. We develop the measure on the basis of only these three factors and apply it to the prediction of the thermal-stability changes upon mutations. As a consequence, an approach toward the prediction is obtained. It is distinguished from the previously reported approaches in the following respects: The parameters adjusted in the manner mentioned above are not employed at all, and the entropic EV effect, which is ascribed to the translational displacement of water molecules coexisting with the protein in the system, is fully taken into account using a molecular model for water. Our approach is compared with one of the most popular approaches, FOLD-X, in terms of the prediction performance not only for single mutations but also for double, triple, and higher-fold (up to sevenfold) mutations. It is shown that on the whole our approach and FOLD-X exhibit almost the same performance despite that the latter uses the adjusting parameters. For multiple mutations, however, our approach is far superior to FOLD-X. Five multiple mutations for staphylococcal nuclease lead to highly enhanced stabilities, but we find that this high enhancement arises from the entropic EV effect. The neglect of this effect in FOLD-X is a principal reason for its ill success. A conclusion is that the three factors mentioned above play essential roles in elucidating the thermal-stability changes upon mutations.

    DOI: 10.1063/1.4931814

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  • Mechanism of One-to-Many Molecular Recognition Accompanying Target-Dependent Structure Formation: For the Tumor Suppressor p53 Protein as an Example 査読 国際誌

    Tomohiko Hayashi, Hiraku Oshima, Satoshi Yasuda, Masahiro Kinoshita

    The Journal of Physical Chemistry B   119   14120 - 14129   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.jpcb.5b08513

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  • Water-mediated forces between the nucleotide binding domains generate the power stroke in an ABC transporter 査読 国際誌

    Tomoka Furukawa-Hagiya, Norio Yoshida, Shuntaro Chiba, Tomohiko Hayashi, Tadaomi Furuta, Yoshiro Sohma, Minoru Sakurai

    Chemical Physics Letters   616-617   165 - 170   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cplett.2014.10.038

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  • ATP-Induced Conformational Changes of Nucleotide-Binding Domains in an ABC Transporter. Importance of the Water-Mediated Entropic Force 査読 国際誌

    Tomohiko Hayashi, Shuntaro Chiba, Yusuke Kaneta, Tadaomi Furuta, Minoru Sakurai

    The Journal of Physical Chemistry B   118   12612 - 12620   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/jp507930e

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  • Physical origins of the high structural stability of CLN025 with only ten residues 査読 国際誌

    Satoshi Yasuda, Tomohiko Hayashi, Masahiro Kinoshita

    The Journal of Chemical Physics   141 ( 10 )   105103   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AIP Publishing  

    CLN025, a peptide with only 10 residues, folds into a specific β-hairpin structure (this is referred to as "native structure"). Here we investigate the stabilization mechanism for CLN025 using our free-energy function F. F comprises two components, the hydration entropy and the component related to the energetic dehydration effect. The former component is calculated using the hybrid of the angle-dependent integral equation theory (ADIET) and our recently developed morphometric approach. The ADIET is a statistical-mechanical theory applied to a molecular model for water. The latter component is calculated in a simple but judicious manner accounting for physically the most important factors: the break of polypeptide-water hydrogen bonds and formation of polypeptide intramolecular hydrogen bonds upon structural change to a more compact one. We consider the native structure, compact nonnative structures newly generated, and a set of random coils mimicking the unfolded state. F and its components are calculated for all the structures considered. The loss of the polypeptide conformational entropy upon structural transition from the unfolded state to a compact structure is also estimated using a simple but physically reasonable manner. We find that the key factor is the water-entropy gain upon folding originating primarily from an increase in the total volume available to the translational displacement of water molecules in the system, which is followed by the reduction of water crowding. The amino-acid sequence of CLN025 enables it not only to closely pack the backbone and side chains including those with large aromatic groups but also to assure the intramolecular hydrogen bonding upon burial of a donor and an acceptor when the backbone forms the native structure. The assurance leads to essentially no enthalpy increase upon folding. The close packing brings a water-entropy gain which is large enough to surpass the conformational-entropy loss. By contrast, it is not possible for the design template of CLN025, GPM12, to realize the same type of structure formation. There are significantly many compact structures which are equally stable in terms of F, and due to the conformational-entropy effect, the unfolded state is favorably stabilized.

    DOI: 10.1063/1.4894753

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  • Binding of an RNA aptamer and a partial peptide of a prion protein: crucial importance of water entropy in molecular recognition 査読 国際誌

    Tomohiko Hayashi, Hiraku Oshima, Tsukasa Mashima, Takashi Nagata, Masato Katahira, Masahiro Kinoshita

    Nucleic Acids Research   42 ( 11 )   6861 - 6875   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press  

    It is a central issue to elucidate the new type of molecular recognition accompanied by a global structural change of a molecule upon binding to its targets. Here we investigate the driving force for the binding of R12 (a ribonucleic acid aptamer) and P16 (a partial peptide of a prion protein) during which P16 exhibits the global structural change. We calculate changes in thermodynamic quantities upon the R12-P16 binding using a statistical-mechanical approach combined with molecular models for water which is currently best suited to studies on hydration of biomolecules. The binding is driven by a water-entropy gain originating primarily from an increase in the total volume available to the translational displacement of water molecules in the system. The energy decrease due to the gain of R12-P16 attractive (van der Waals and electrostatic) interactions is almost canceled out by the energy increase related to the loss of R12-water and P16-water attractive interactions. We can explain the general experimental result that stacking of flat moieties, hydrogen bonding and molecular-shape and electrostatic complementarities are frequently observed in the complexes. It is argued that the water-entropy gain is largely influenced by the geometric characteristics (overall shapes, sizes and detailed polyatomic structures) of the biomolecules.

    DOI: 10.1093/nar/gku382

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  • Dynamics and structural changes induced by ATP and/or substrate binding in the inward-facing conformation state of P-glycoprotein 査読 国際誌

    Yurika Watanabe, Wei-Lin Hsu, Shuntaro Chiba, Tomohiko Hayashi, Tadaomi Furuta, Minoru Sakurai

    Chemical Physics Letters   557   145 - 149   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cplett.2012.12.040

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  • Full-Quantum chemical calculation of the absorption maximum of bacteriorhodopsin: a comprehensive analysis of the amino acid residues contributing to the opsin shift 査読 国際誌

    Tomohiko Hayashi, Azuma Matsuura, Hiroyuki Sato, Minoru Sakurai

    BIOPHYSICS(Biophysics and Physicobiology)   8   115 - 125   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Biophysical Society of Japan  

    Herein, the absorption maximum of bacteriorhodopsin (bR) is calculated using our recently developed method in which the whole protein can be treated quantum mechanically at the level of INDO/S-CIS//ONIOM (B3LYP/6-31G(d,p): AMBER). The full quantum mechanical calculation is shown to reproduce the so-called opsin shift of bR with an error of less than 0.04 eV. We also apply the same calculation for 226 different bR mutants, each of which was constructed by replacing any one of the amino acid residues of the wild-type bR with Gly. This substitution makes it possible to elucidate the extent to which each amino acid contributes to the opsin shift and to estimate the inter-residue synergistic effect. It was found that one of the most important contributions to the opsin shift is the electron transfer from Tyr185 to the chromophore upon excitation. We also indicate that some aromatic (Trp86, Trp182) and polar (Ser141, Thr142) residues, located in the vicinity of the retinal polyene chain and the <symbol>b</symbol>-ionone ring, respectively, play an important role in compensating for the large blue-shift induced by both the counterion residues (Asp85, Asp212) and an internal water molecule (W402) located near the Schiff base linkage. In particular, the effect of Trp86 is comparable to that of Tyr185. In addition, Ser141 and Thr142 were found to contribute to an increase in the dipole moment of bR in the excited state. Finally, we provide a complete energy diagram for the opsin shift together with the contribution of the chromophore-protein steric interaction.<br>

    DOI: 10.2142/biophysics.8.115

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  • Theoretical Study on the Absorption Maxima of Real GFPs 査読 国際誌

    Azuma Matsuura, Tomohiko Hayashi, Hiroyuki Sato, Atsuya Takahashi, Minoru Sakurai

    Chemical Physics Letters   484   324 - 329   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.cplett.2009.11.074

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  • Accurate Evaluation of the Absorption Maxima of Retinal Proteins Based on a Hybrid QM/MM Method 査読 国際誌

    Azuma Matsuura, Hiroyuki Sato, Hirohiko Houjou, Shino Saito, Tomohiko Hayashi, Minoru Sakurai

    Journal of Computational Chemistry   27 ( 14 )   1623 - 1630   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jcc.20432

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書籍等出版物

  • Statistical Thermodynamics on the Binding of Biomolecules, Part II: Basis of Protein-Ligand and Protein-Protein Interactions, Chapter 13, The Role of Water in ATP Hydrolysis Energy Transduction by Protein Machinery

    Tomohiko Hayashi( 担当: 共著)

    Springer  2018年 

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    記述言語:英語 著書種別:学術書

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MISC

  • Accurate and rapid calculation of hydration free energy and its physical implication for biomolecular functions 招待 査読 国際誌

    Masahiro Kinoshita, Tomohiko Hayashi

    Biophysical Reviews   12   469 - 480   2020年3月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

    DOI: 10.1007/s12551-020-00686-5

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  • Theoretical identification of thermostabilizing amino acid mutations for G-protein-coupled receptors 招待 査読 国際誌

    Takeshi Murata, Satoshi Yasuda, Tomohiko Hayashi, Masahiro Kinoshita

    Biophysical Reviews   12   323 - 332   2020年3月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

    DOI: 10.1007/s12551-020-00678-5

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  • サーモフィリックロドプシンの極めて高い熱安定性に関する統計熱力学的解析 招待

    安田賢司, 林智彦, 村田武士, 木下正弘

    月刊「細胞」   52 ( 2 )   37 - 41   2020年

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:ニュー・サイエンス社  

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受賞

  • 第4回 Biophysics and Physicobiology 論文賞

    2015年   日本生物物理学会   Full-Quantum chemical calculation of the absorption maximum of bacteriorhodopsin: a comprehensive analysis of the amino acid residues contributing to the opsin shift

    林智彦

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    受賞区分:国内外の国際的学術賞  受賞国:日本国

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共同研究・競争的資金等の研究

  • 次世代ペプチド薬の物理理論に基づく高速デザイン法の開発

    研究課題/領域番号:22K03547

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    林 智彦

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • MDM2をターゲットとした新規抗癌剤候補ペプチドの設計・合成

    2019年10月

    制度名:文部科学省卓越研究員事業

    提供機関:文部科学省

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    資金種別:競争的資金

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  • ペプチド抗癌剤の物理理論に基づく高速探索法の開発

    研究課題/領域番号:19K14674

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業

    研究種目:若手研究

    提供機関:日本学術振興会

    林 智彦

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究は、癌原因タンパク質MDM2(抗腫瘍蛋白質p53の働きを阻害する)に強く結合することでMDM2を無効化する「ペプチド抗癌剤候補」の理論による設計・実験による合成を目的とした。
    その成果として、「タンパク質とペプチドの結合自由エネルギーを高速に計算する手法」を開発し、抗MDM2ペプチドの結合メカニズムを解明するとともに、得られた知見をもとに「新規ペプチド抗癌剤候補」を実験により合成することに成功した。さらに、「タンパク質-ペプチド複合体の天然構造を高速に特定する理論手法」の開発を進めることで、ペプチド創薬における新たな基盤の構築へと発展させることができた。

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担当経験のある授業科目(researchmap)

  • 分子生体機能工学特論

    機関名:新潟大学

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  • 研究課題調査I

    機関名:新潟大学

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  • 実践プログラミングII

    機関名:新潟大学

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  • 情報処理演習

    機関名:立命館大学薬学部

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  • 卒業研修I

    機関名:新潟大学

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  • 研究課題調査II

    機関名:新潟大学

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  • リメディアル演習

    機関名:新潟大学

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  • 卒業研究I

    機関名:新潟大学

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  • 実践プログラミングI

    機関名:新潟大学

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  • 工学リテラシー入門(融合領域分野)

    機関名:新潟大学

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  • 人間支援感性科学概論

    機関名:新潟大学

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  • 機能生理学

    機関名:新潟大学

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  • 実践物理学演習

    機関名:新潟大学

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  • 技術英語

    機関名:新潟大学

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担当経験のある授業科目

  • 実践物理学演習

    2022年
    -
    現在
    機関名:新潟大学

  • バイオメカニクス

    2022年
    機関名:新潟大学

  • 自然科学総論III

    2022年
    機関名:新潟大学

  • 機能生理学

    2021年
    -
    現在
    機関名:新潟大学

  • 総合技術科学演習

    2021年
    -
    現在
    機関名:新潟大学

  • 機械システム論

    2021年
    機関名:新潟大学

  • 卒業研修II

    2020年
    -
    現在
    機関名:新潟大学

  • 実践プログラミングII

    2020年
    -
    現在
    機関名:新潟大学

  • 人間支援感性科学概論

    2020年
    -
    現在
    機関名:新潟大学

  • 卒業研修I

    2020年
    -
    現在
    機関名:新潟大学

  • 工学リテラシー入門(融合領域分野)

    2020年
    -
    現在
    機関名:新潟大学

  • 卒業研究II

    2020年
    -
    現在
    機関名:新潟大学

  • 卒業研究I

    2020年
    -
    現在
    機関名:新潟大学

  • 技術英語

    2020年
    -
    現在
    機関名:新潟大学

  • 実践プログラミングI

    2020年
    -
    現在
    機関名:新潟大学

  • 分子生体機能工学特論

    2020年
    -
    現在
    機関名:新潟大学

  • 研究課題調査I

    2020年
    -
    現在
    機関名:新潟大学

  • 研究課題調査II

    2020年
    -
    現在
    機関名:新潟大学

  • リメディアル演習

    2020年
    機関名:新潟大学

▶ 全件表示