Molecular dynamics simulations on membrane transporting proteins

• Project/Area Number: 15083201
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research (2007-2008); The University of Tokyo (2003-2006)
• Principal Investigator: SUGITA Yuji The Institute of Physical and Chemical Research, 杉田理論生物化学研究室, 准主任研究員 (80311190)
• Co-Investigator(Kenkyū-buntansha): KONDOU Youhei 東京大学, 分子細胞生物学研究所, 助手 (30436604)
• Project Period (FY): 2003 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥88,800,000 (Direct Cost: ¥88,800,000); Fiscal Year 2008: ¥16,100,000 (Direct Cost: ¥16,100,000); Fiscal Year 2007: ¥16,100,000 (Direct Cost: ¥16,100,000); Fiscal Year 2006: ¥15,500,000 (Direct Cost: ¥15,500,000); Fiscal Year 2005: ¥15,600,000 (Direct Cost: ¥15,600,000); Fiscal Year 2004: ¥17,000,000 (Direct Cost: ¥17,000,000); Fiscal Year 2003: ¥8,500,000 (Direct Cost: ¥8,500,000)
• Keywords: 膜蛋白質 / 分子動力学計算 / イオンポンプ / トランスロコン / 膜タンパク質 / 物質輸送 / シミュレーション / 膜透過装置 / 分子動力学 / 生体膜 / プロトン化 / 拡張アンサンブル法 / イオン能動輸送 / 分子動力学法

Research Abstract

生体膜を隔てたイオンやタンパク質の物質輸送を行う膜輸送タンパク質の立体構造を用いた分子動力学計算を行うことにより膜タンパク質の構造変化と物質輸送機構の関係を明らかにした。ターゲットとして、カルシウムイオンポンプ、その機能を制御するフォスフォランバン、タンパク質輸送を行うSecトランスロコンを選び、脂質二重膜と溶媒を露わに含む全原子分子動力学計算を実施することにより、膜インターフェイスにおけるSoftな相互作用がこれらのタンパク質の機能に果たす役割を明らかにすることができた。

Research Products

• [Journal Article] Transmembrane Structures of Amyloid Precursor Protein Dimer Predicted by Replica-Exchange Molecular Dynamics Simulations (2009)
  • Author(s): N. Miyashita, J. E. Straub, D. Thirumalai, Y. Sugita
  • Journal Title: J. Am. Chem. Soc. 131(10) Pages: 3438-3439
  • Peer Reviewed
• [Journal Article] Free-energy landscapes of proteins in solution by generalized-ensemble simulations (2009)
  • Author(s): Y. Sugita
  • Journal Title: Frontiers in Bioscience 14 Pages: 1292-1303
  • Peer Reviewed
• [Journal Article] Mg^<2+>-sensing mechanism of Mg^<2+> transporter MgtE probed by molecular dynamics study (2008)
  • Author(s): R. Ishitani, Y. Sugita, N. Dohmae, N. Furuya, M. Hattori, O. Nureki
  • Journal Title: Proc. Natl. Acad. Sci. USA. 105(40) Pages: 15393-15398
  • Peer Reviewed
• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): T. Tsukazaki, H. Mori, S. Fukai, R. Ishitani, T. Mori, N. Dohmae, A. Perederina, Y. Sugita, D.G. Vassylyev, K. Ito, O. Nureki
  • Journal Title: Nature 455 Pages: 938-992
  • Peer Reviewed
• [Journal Article] Generalized-Ensemble Algorithms for Protein Folding Simulations (2008)
  • Author(s): Y. Sugita, A. Mitsutake, Y. Okamoto
  • Journal Title: Lecture Notes in Physics 736 Pages: 369-407
  • Peer Reviewed
• [Journal Article] 生体分子の構造探索の理論 (2008)
  • Author(s): 杉田有治
  • Journal Title: 化学と工業 61-6 Pages: 582-584
  • Peer Reviewed
• [Journal Article] カルシウムポンプの機能制御機構 (2008)
  • Author(s): 杉田有治
  • Journal Title: 生化学 61-6 Pages: 582-584
  • NAID: 10022594597
  • Peer Reviewed
• [Journal Article] ぞくぞくとわかってきた膜を隔てたイオン輸送装置構造 (2008)
  • Author(s): 杉田有治
  • Journal Title: 生物物理 48(6) Pages: 330-332
  • Peer Reviewed
• [Journal Article] Mg^<2+>-sensing mechanism of Mg^<2+> transporter MgtE probed by molecular dynamics study (2008)
  • Author(s): R. Ishitani, et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 105 (40) Pages: 15393-15398
  • Peer Reviewed
• [Journal Article] Conformational transition of Sec machinery inferred from bacterial SecYE structures (2008)
  • Author(s): T. Tsukazaki, et al.
  • Journal Title: Nature. Pages: 455988-992
  • Peer Reviewed
• [Journal Article] カルシウムポンプの機能制御機構 (2008)
  • Author(s): 杉田 有治
  • Journal Title: 生化学 80 Pages: 917-924
  • NAID: 10022594597
• [Journal Article] New implementation of a combined quantum mechanical and molecular mechanical method using modified generalized hybrid orbitals (2007)
  • Author(s): J. Jung, C.H. Choi, Y. Sugita, S. Ten-no
  • Journal Title: J. Chem. Phys. 127 Pages: 204102-204102
  • Peer Reviewed
• [Journal Article] Replica-exchange molecular dynamics simulations of diffracted X-ray tracking (2007)
  • Author(s): Y. Kawashima, Y.C. Sasaki, Y. Sugita, T. Yoda, Y. Okamoto
  • Journal Title: Molecular simulation 33 Pages: 97-102
  • Peer Reviewed
• [Journal Article] Physical basis for characterizing native structures of proteins (2007)
  • Author(s): Y. Harano, R. Roth, Y. Sugita, M. Ikeguchi, M. Kinoshita
  • Journal Title: Chem. Phys. Lett. 437 Pages: 112-116
  • Peer Reviewed
• [Journal Article] Cooperative Folding Mechanism of a b-Hairpin Peptide Studied by Using a Multicanonical Replica-Exchange Molecular Dynamics Simulation (2007)
  • Author(s): Yoda T, Sugita Y, Okamoto Y
  • Journal Title: PROTEINS : Structure, Function, and Bioinformatics 66 Pages: 846-859
  • Peer Reviewed
• [Journal Article] New implementation of a combined quantum mechanical and molecular mechanical method using modified generalized hybrid orbitals. (2007)
  • Author(s): J. Jung, et. al.
  • Journal Title: J. Chem. Phys. 127 Pages: 204102-204102
  • Peer Reviewed
• [Journal Article] Replica-exchange molecular dynamics simulations of diffracted X-ray tracking. (2007)
  • Author(s): Y. Kawashima, et. al.
  • Journal Title: Molecular simulation 33 Pages: 97-102
  • Peer Reviewed
• [Journal Article] Physical basis for characterizing native structures of proteins. (2007)
  • Author(s): Y. Harano, et. al.
  • Journal Title: Chem. Phys. Lett. 437 Pages: 112-116
  • Peer Reviewed
• [Journal Article] Cooperative Folding Mechanism of a b-Hairpin Peptide Studied by Using a Multicanonical Replica-Exchange Molecular Dynamics Simulation. (2007)
  • Author(s): Yoda et al.
  • Journal Title: PROTEINS : Structure, Function, and Bioinformatics 66
• [Journal Article] Structural Changes in the Cytoplasmic Domain of Phospholamban by Phosphorylation at Ser16 : A Molecular Dynamics Study (2006)
  • Author(s): Sugita Y, Miyashita N, Yoda T, Ikeguchi M, Toyoshima C
  • Journal Title: Biochemistry 45 Pages: 11752-11761
  • Peer Reviewed
• [Journal Article] 膜蛋白質の分子動力学 (2006)
  • Author(s): 杉田有治, 池口満徳
  • Journal Title: 物性研究 50 Pages: 1271-1277
  • Peer Reviewed
• [Journal Article] Structural Changes in the Cytoplasmic Domain of Phospholamban at Serl6 : A Molecular Dynamics Study (2006)
  • Author(s): Sugita et al.
  • Journal Title: Biochemistry 45 Pages: 11752-11761
• [Journal Article] 膜蛋白質の分子動力学 (2006)
  • Author(s): 杉田 有治 et al.
  • Journal Title: 物性研究 50 Pages: 1271-1277
• [Journal Article] Protonation of the acidic residues in the transmembrane cation-binding sites of the Ca^<2+>-pump (2005)
  • Author(s): Sugita Y, Miyashita N, Ikeguchi M, Kidera A, Toyoshima C
  • Journal Title: J. Am. Chem. Soc. 127 Pages: 6150-6151
  • Peer Reviewed
• [Journal Article] Structural role of countertransport revealed in Ca^<2+> pump crystal structure in the absence of Ca^<2+> (2005)
  • Author(s): Obara K, Miyashita N, Xu C, Toyoshima I, Sugita Y, Ineshi G, Toyoshima C
  • Journal Title: Proc. Natl. Acid, Sci. USA. 102 Pages: 14489-14496
  • Peer Reviewed
• [Journal Article] カルシウムポンプの構造と機能 (2005)
  • Author(s): 杉田有治, 豊島近
  • Journal Title: 蛋白質・核酸・酵素, 増刊号「生命秩序を担う生体超分子」 50 Pages: 1271-1277
  • Peer Reviewed
• [Journal Article] Molecular mechanism for stabilizing a short helical peptide studied by generalized-ensemble simulations with explicit solvent (2005)
  • Author(s): Sugita Y, Okamoto Y
  • Journal Title: Biophysical J. 88 Pages: 3180-3190
  • Peer Reviewed
• [Journal Article] Molecular dynamics simulations of DNA dimers based on replica-exchange umbrella sampling. I. Test of sampling efficiency (2005)
  • Author(s): Murata K, Sugita Y, Okamoto Y
  • Journal Title: J. Theor. Comp. Chem. 4 Pages: 411-432
  • Peer Reviewed
• [Journal Article] Molecular dynamics simulations of DNA dimers based on replica-exchange umbrella sampling. II. Free energy analysis (2005)
  • Author(s): Murata K, Sugita Y, Okamoto Y
  • Journal Title: J. Theor. Comp. Chem. 4 Pages: 433-448
  • Peer Reviewed
• [Journal Article] Structures of a peptide fragment of β_2-microgloblin studied by replica-exchange molecular dynamics simulations : towards the understanding of the mechanism of amyloid formation (2005)
  • Author(s): Nishino M, Sugita Y, Yoda T, Okamoto Y
  • Journal Title: FEBS Lett. 579 Pages: 5425-5429
  • Peer Reviewed
• [Journal Article] Effects of the Fixed End in Single-Molecular Imaging Techiques : A Replica Exchange Molecular Dynamics Simulation (2005)
  • Author(s): Kawashima Y, Sugita Y, Yoda T, Okamoto Y
  • Journal Title: Chem. Phys. Lett. 414 Pages: 449-455
  • Peer Reviewed
• [Journal Article] Protonation of the acidic residues in the transmembrane cation-binding sites of the Ca^<2+>-pump (2005)
  • Author(s): Sugita et al.
  • Journal Title: J.Am.Chem.Soc. 127 Pages: 6150-6151
• [Journal Article] Structural role of countertransport revealed in Ca^<2+> pump crystal structure in the absence of Ca^<2+>. (2005)
  • Author(s): Obara et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 102 Pages: 14489-14496
• [Journal Article] Molecular mechanism for stabilizing a short helical peptide studied by generalized-ensemble simulations with explicit solvent. (2005)
  • Author(s): Sugita et al.
  • Journal Title: Biophys.J. 88 Pages: 3180-3190
• [Journal Article] Molecular dynamics simulations of DNA dimers based on replica-exchange umbrella sampling.I.Test of sampling efficiency. (2005)
  • Author(s): Murata et al.
  • Journal Title: J.Theor.Comp.Chem. 4 Pages: 411-432
• [Journal Article] Molecular dynamics simulations of DNA dimers based on replica-exchange umbrella sampling.II.Free energy analysis. (2005)
  • Author(s): Murata et al.
  • Journal Title: J.Theor.Comp.Chem. 4 Pages: 433-448
• [Journal Article] Structures of a peptide fragment of β_2-microgloblin studied by replica-exchange molecular dynamics simulations : towards the understanding of the mechanism of amyloid formation. (2005)
  • Author(s): Nishino et al.
  • Journal Title: FEBS Lett. 579 Pages: 433-448
• [Journal Article] Secondary-Structure Preferences of Force Fields for Proteins Evaluated by Generalized-Ensemble Simulations (2004)
  • Author(s): T. Yoda, Y. Sugita, Y. Okamoto
  • Journal Title: Chem. Phys. Pages: 269-283
  • Peer Reviewed
• [Journal Article] Comparisons of Force Fields for Proteins by Generalized-Ensemble Simulations (2004)
  • Author(s): T. Yoda, Y. Sugita, Y. Okamoto
  • Journal Title: Chem. Phys. Lett. 386 Pages: 460-467
  • Peer Reviewed
• [Journal Article] Free energy calculations for DNA base stacking by replica-exchange umbrella sampling (2004)
  • Author(s): K. Murata, Y. Sugita, Y. Okamoto
  • Journal Title: Chem. Phys. Lett. 385 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Secondary-Structure Preferences of Force Fields for Proteins Evaluated by Generalized-Ensemble Simulations (2004)
  • Author(s): Yoda, T. et al.
  • Journal Title: Chem.Phys. 307 Pages: 269-283
• [Journal Article] Comparisons of Force Fields for Proteins by Generalized-Ensemble Simulations (2004)
  • Author(s): Yoda, T. et al.
  • Journal Title: Chem.Phys.Lett. 386 Pages: 460-467
• [Journal Article] Free energy calculations for DNA base stacking by replica-exchange umbrella sampling (2004)
  • Author(s): Murata, K. et al.
  • Journal Title: Chem.Phys.Lett. 385 Pages: 1-7
• [Presentation] Molecular Dynamics Simulations of Soft Interactions at the Membrane Interface (2009)
  • Author(s): 杉田有治
  • Organizer: International Symposium on Molecular Soft Interactions in Biological Systems
  • Place of Presentation: 大阪
• [Presentation] 膜蛋白質の分子動力学計算 (2009)
  • Author(s): 杉田有治
  • Organizer: 計算科学研究センター・ワークショップ
  • Place of Presentation: 岡崎
• [Presentation] 分子シミュレーションからカルシウムポンプの構造柔軟性を考える (2008)
  • Author(s): 杉田 有治
  • Organizer: 日本生物物理学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-12-22
• [Presentation] Molecular Dynamics Study of Sarcoplasmic Reticulum Calcium Pump (2008)
  • Author(s): 杉田 有治
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2008-12-09
• [Presentation] Protein-Lipid Interactions Revealed by Molecular Dynamics Simulations (2008)
  • Author(s): 杉田有治
  • Organizer: 九州大学次世代研究スーパースター養成プログラム公開シンポジウム
  • Place of Presentation: 博多
• [Presentation] Molecular Dynamics simulations of protein dynamics in biological membrane (2008)
  • Author(s): 杉田有治
  • Organizer: 次世代ナノ情報機能・材料グループ成果報告会
  • Place of Presentation: 仙台
• [Presentation] Molecular Dynamics Study of Sarcoplasmic Reticulum Calcium Pump (2008)
  • Author(s): Yuji Sugita
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 (BMB2008)
  • Place of Presentation: 神戸
• [Presentation] Toward a complete understanding of molecular mechanism of ion transport by membrane proteins (2008)
  • Author(s): Yuji Sugita
  • Organizer: 1st Joint Workshop on Computational Science
  • Place of Presentation: 和光
• [Presentation] Molecular mechanism for stabilizing Ca^<2+> at the transmembrane binding sites in Ca^<2+>-pump (2008)
  • Author(s): Yuji Sugita
  • Organizer: 1st CMD International Symposium Chemical Computations
  • Place of Presentation: Seoul
• [Presentation] カルシウムポンプの機能発現機構に関する分子動力学計算 (2008)
  • Author(s): 杉田有治
  • Organizer: 日本物理学会第63回年次大会
  • Place of Presentation: 東大阪
• [Presentation] 分子シミュレーションからカルシウムポンプの構造柔軟性を考える (2007)
  • Author(s): 杉田有治
  • Organizer: 日本生物物理学会第45回年会
  • Place of Presentation: 横浜
• [Presentation] Molecular Dynamics Simulations on the Conformational Stability of the Ca^<2+>-binding sites in Ca^<2+>-pump (2007)
  • Author(s): Yuji Sugita
  • Organizer: BNL-RIKEN Life Science Workshop
  • Place of Presentation: Upton
• [Presentation] カルシウムポンプによるイオン能動輸送の分子機構 (2007)
  • Author(s): 杉田有治
  • Organizer: 理研シンポジウム「計算機と生物学 in Silico Biology」
  • Place of Presentation: 和光
• [Presentation] SR Ca^<2+>-ATPaseによるCa^<2+>輸送とプロトン対抗輸送の分子機構 (2006)
  • Author(s): 杉田有治
  • Organizer: 第4回特定領域研究「膜インターフェイス」公開シンポジウム
  • Place of Presentation: 京都大学百周年記念ホール
  • Year and Date: 2006-07-05
• [Presentation] レプリカ交換法による蛋白質機能解析 (2006)
  • Author(s): 杉田有治
  • Organizer: 第6回蛋白質科学会年会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2006-04-26
• [Presentation] 分子動力学計算による蛋白質原子揺らぎの収束性について (2006)
  • Author(s): 杉田有治
  • Organizer: 大阪大学蛋白研セミナー
  • Place of Presentation: 大阪大学蛋白質研究所
• [Presentation] Molecular dynamics simulations of sarcoplasimc reticulum calcium pump in membrane (2006)
  • Author(s): Yuji Sugita
  • Organizer: In Satellite meeting for 20^<th> IUBMB International Congress of Biochemistry and Molecular Biology & 11^<th> FAOBMB Congress on Molecular Mechanism and Regulation in Cation Transport ATPases and Related Genetic Diseases
  • Place of Presentation: 京都リサーチパーク
• [Presentation] 分子動力学計算によるカルシウムポンプの機能制御機構の解析 (2006)
  • Author(s): 杉田有治
  • Organizer: 大阪大学蛋白研セミナー
  • Place of Presentation: 大阪大学蛋白質研究所
• [Presentation] カルシウムポンプとその阻害剤の分子動力学計算 (2006)
  • Author(s): 杉田有治
  • Organizer: スーパーコンピュータワークショップ
  • Place of Presentation: 自然科学機構・岡崎共通研究施設・計算科学研究センター
• [Presentation] Theoretical studies on the proton countertransport by sarcoplasmic reticulum calcium pump (2006)
  • Author(s): Yuji Sugita
  • Organizer: In KAIST seminar
  • Place of Presentation: KAIST、Korea
• [Presentation] カルシウムポンプの分子動力学計算 : 構造から機能の理解へ (2006)
  • Author(s): 杉田有治
  • Organizer: 京都大学ウイルス研セミナー
  • Place of Presentation: 京都大学ウイルス研究所
• [Presentation] 筋小胞体Ca^<2+>-ATPaseの機能に関する分子動力学計算 (2005)
  • Author(s): 杉田有治
  • Organizer: 第28回日本分子生物学会年会
  • Place of Presentation: 福岡ドーム
• [Presentation] Molecular dynamics studies on the biological functions of sarcoplasmic reticulum Ca^<2+>-ATPase. (2005)
  • Author(s): Yuji Sugita
  • Organizer: In P-Chem seminar
  • Place of Presentation: Boston University、Boston
• [Presentation] SR Ca^<2+>-ATPase Atomic Structure and Molecular Dynamics Simulations (2005)
  • Author(s): Yuji Sugita, Chikashi Toyoshima
  • Organizer: In 11-th International ATPase Conference and 59-th Annual Meeting and Symposium of the Society of General Physiologists
  • Place of Presentation: Marine Biological Laboratory, Woods Hole, Massachusetts
• [Presentation] 脂質二重膜中におけるカルシウムポンプの運動と機能 (2005)
  • Author(s): 杉田有治
  • Organizer: 生体分子ダイナミックス研究会
  • Place of Presentation: 東京大学農学部
• [Presentation] Molecular dynamics studies on Sarcoplasmic reticulum Ca^<2+>-ATPase (2005)
  • Author(s): Yuji Sugita
  • Organizer: In Theoretical Biophysics Seminar
  • Place of Presentation: Rutgars University, New Jersey
• [Presentation] Molecular dynamics simulations SR Ca^<2+>-ATPase in the Ca^<2+>-bound and unbound states (2005)
  • Author(s): Yuji Sugita, Chikashi Toyoshima
  • Organizer: In 2005 FASEB Summer Research Conferences
  • Place of Presentation: Vermont Academy, Saxton River, Vermont, USA
• [Presentation] Molecular Mechanism of cooperative Ca^<2+>-binding by Ca2+-ATPase, insight from molecular dynamics simulations (2005)
  • Author(s): Yuji Sugita
  • Organizer: In the 2^<nd> symposium of membrane interface
  • Place of Presentation: ホテル阪急エキスポパーク
• [Presentation] 脂質二重膜中でのカルシウムポンプの分子動力学 (2004)
  • Author(s): 杉田有治
  • Organizer: 第1回特定領域研究「膜インターフェイス」公開シンポジウム
  • Place of Presentation: 東京大学山上会館
• [Book] Rugged Free Energy Landscapes (2008)
  • Author(s): Y. Sugita, et al.
  • Total Pages: 412
  • Publisher: Springer
• [Publications] Mitsutake et al.: "Replica-exchange multicanonical and multicanonical replica-exchange Monte Carlo simulations of peptide I.Formulation and benchmark test"J.Chem.Phys.. 118. 6664-6675 (2003)
• [Publications] Mitsutake, A. et al.: "Replica-exchange multicanonical and multicanonical replica-exchange Monte Carlo simulations of peptide II.Application to a more complex system"J.Chem.Phys.. 118. 6676-6688 (2003)
• [Publications] Funahashi J. et al.: "How can free energy component analysis explain the difference in protein stability caused by amino acid substitutions?"Protein Eng. 16. 665-671 (2003)