拡張アンサンブル法による蛋白質折り畳み機構の研究

• Project/Area Number: 15076213
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Nagoya University (2005-2007); Institute for Molecular Science (2004); Okazaki National Research Institutes (2003)
• Principal Investigator: 岡本 祐幸 Nagoya University, 大学院・理学研究科, 教授 (70185487)
• Co-Investigator(Kenkyū-buntansha): 奥村 久士 (奥村 久志) 名古屋大学, 大学院・理学研究科, 特任講師 (80360337)
• Project Period (FY): 2003 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥30,000,000 (Direct Cost: ¥30,000,000); Fiscal Year 2007: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2006: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2005: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2004: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
• Keywords: タンパク質の折り畳み / 分子シミュレーション / 分子動力学法 / 拡張アンサンブル法 / マルチカノニカル法 / 計算機シミュレーション / モンテカルロ法 / レプリカ交換法 / マルチバーリック法 / 膜タンパク質 / 蛋白質 / 折り畳み / 立体構造予測

Research Abstract

本年度の主な研究成果は以下のとおりである。
1.拡張アンサンブル法の一つであるマルチカノニカル法とマルチオーバーラップ法の利点を合体させた、マルチカノニカル・マルチオーバーラップ法を開発した。
2.今回開発したマルチカノニカル・マルチオーバーラップ法をアルツハイマー病の原因ペプチドである、アミロイドβペプチドの29番目から42番目のアミノ酸残基に対応するペプチドフラグメント2個の系に適用して、アミロイド形成の初期過程を考察した。2つのペプチドフラグメントが空間的に離れているときは、αヘリックスやβヘアピン構造をしているが、それらが近づいてくると、2次構造がこわされて、βストランド状にまっすぐに伸びた構造が結合して、2本のβストランドが水素結合でβシート構造を作ることが示唆された。アミロイド線維はこのβシート構造が更に結合して形成されると推測された。
3.数年前にわれわれが開発した拡張アンサンブル法である、マルチバーリック・マルチサーマル法は、エネルギーと体積の2次元空間でランダムウォークする手法であり、特に、タンパク質の高圧変性を研究するのに適した手法である。我々は、昨年に続き、水中のアラニンジペプチドの系にこの手法を適用して、この系の高圧実験の結果と比較した。今年は、この計算にAMBER99とAMBER96の2つのポテンシャルエネルギーを使った。我々の以前の研究のより、前者はαヘリックスを後者はβシートを作り過ぎる傾向があることが分かっている。ラーマン散乱の実験によって、得られた部分モルエンタルピーや部分モル体積は、ちょうど、これらの2つのエネルギー関数で得られた計算結果の中間にあることが判明した。理想的なエネルギー関数はこれら2つのエネルギー関数の中間的なものに対応することが示唆された

Research Products

• [Journal Article] Multibaric-multithermal molecular dynamics simulation of alanine dipe ptide in explicit water (2007)
  • Author(s): H. Okumura & Y. Okamoto
  • Journal Title: Bulletin of the Chemical Society of Japan 80 Pages: 1114-1123
  • Peer Reviewed
• [Journal Article] Effective sampling in the configurational space of a small peptide by the multicanonical-multioverlap algorithm (2007)
  • Author(s): S.G. Itoh & Y. Okamoto
  • Journal Title: Physical Review E 76 Pages: 2670510-2670510
  • NAID: 120006545922
  • Peer Reviewed
• [Journal Article] Normal mode analysis of polytheonamide B (2007)
  • Author(s): T. Mori, H. Kokubo, H. Shimizu, M. Iwamoto, S. Oiki, & Y. Okamoth
  • Journal Title: Journal of the Physical Society of Japan 76 Pages: 9480110-9480110
  • Peer Reviewed
• [Journal Article] Cooperative folding mechanism of a β-hairpin peptide studied by a multicanonical replica-exchange molecular dynamics simulation (2007)
  • Author(s): T.Yoda, Y.Sugita, Y Okamoto
  • Journal Title: PROTEINS : Structure, Function, and Bioinformatics 66 Pages: 846-859
• [Journal Article] Generalized-ensemble algorithms for molecular dynamics simulations (2007)
  • Author(s): S.G.Itoh, H.Okumura, Y.Okamoto
  • Journal Title: Molecular Simulation 33 Pages: 47-56
• [Journal Article] A new generalized-ensemble algorithm : multicanonical-multioverlap algorithm (2007)
  • Author(s): S.G.Itoh, Y.Okamoto
  • Journal Title: Molecular Simulation 33 Pages: 83-90
• [Journal Article] Multibaric-multithermal molecular dynamics simulation : generalized Nose-Poincare-Andersen method (2007)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Molecular Simulation 33 Pages: 91-96
• [Journal Article] Replica-exchange moleculr dynamics simulation 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
• [Journal Article] Explicit symplectic integrators of molecular dynamics algorithms for rigid-body molecules in the canonical, isobaric-isothermal, and related ensembles (2007)
  • Author(s): H.Okumura, S.G.Itoh, Y.Okamoto
  • Journal Title: Journal of Chemical Physics 126
  • NAID: 120006545076
• [Journal Article] Residual entropy of ordinary ice from multicanonical simulations (2007)
  • Author(s): B.A.Berg, C.Muguruma, Y.Okamoto
  • Journal Title: Physical Review B 75
  • NAID: 120006545083
• [Journal Article] Theoretical studies of transition states by the multioverlap molecular dynamics methods (2006)
  • Author(s): S.G.Itoh, Y.Okamoto
  • Journal Title: Journal of Chemical Physics 124
  • NAID: 120000975328
• [Journal Article] Secondary-structure design of proteins by a backbone torsion energy (2006)
  • Author(s): Y.Sakae, Y.Okamoto
  • Journal Title: Journal of Physical Society of Japan 75
  • NAID: 110004702343
• [Journal Article] 生体系における大規模分子シミュレーション (2006)
  • Author(s): 岡本祐幸
  • Journal Title: 応用数理 16 Pages: 15-19
• [Journal Article] Replica-exchange methods and predictions of helix configuration of membrane proteins (2006)
  • Author(s): H.Kokubo, Y.Okamoto
  • Journal Title: Molecular Simulation 32 Pages: 791-801
• [Journal Article] 拡張アンサンブル法による膜タンパク質の立体構造予測 (2006)
  • Author(s): 小久保裕功, 岡本祐幸
  • Journal Title: 統計数理 54 Pages: 211-222
  • NAID: 120006019067
• [Journal Article] Multibaric-multithermal ensemble molecular dynamics simulations (2006)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Journal of Computational Chemistry 27 Pages: 379-395
• [Journal Article] Molecular mechanism for stabilizing a short helical peptide studied by generalized-ensemble simulations with explicit solvent (2005)
  • Author(s): Y.Sugita, Y.Okamoto
  • Journal Title: Biophysical Journal 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): K.Murata, Y.Sugita, Y.Okamoto
  • Journal Title: Journal of Theoretical & Computational Chemistry 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, Y.Sugita, Y.Okamoto
  • Journal Title: Journal of Theoretical & Computational Chemistry 4 Pages: 433-448
• [Journal Article] Replica-exchange molecular dynamics simulation of small peptide in water and in ethanol (2005)
  • Author(s): K.Yoshida, T.Yamaguchi, Y.Okamoto
  • Journal Title: Chemical Physics Letters 412 Pages: 280-284
• [Journal Article] Structures of a peptide fragment of β2-microglobulin studied by replica-exchange molecular dynamics simulations - towards the understanding of the mechanism of amyloid formation (2005)
  • Author(s): M.Nishino, Y.Sugita, T.Yoda, Y.Okamoto
  • Journal Title: FEBS Letters 579 Pages: 5425-5429
• [Journal Article] Effects of the fixed end in single-molecule imaging techniques : A replica-exchange molecular dynamics study (2005)
  • Author(s): Y.Kawashima, Y.Sugita, T.Yoda, Y.Okamoto
  • Journal Title: Chemical Physics Letters 414 Pages: 449-455
• [Journal Article] Multibaric-multithermal ensemble simulations for fluid systems (2005)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Physica A 350 Pages: 150-158
• [Journal Article] Molecular simulations in the multibaric-multithermal ensembles (2005)
  • Author(s): H.Okurnura, Y.Okamoto
  • Journal Title: Computer Physics Communications 169 Pages: 317-321
• [Journal Article] PDBデータベースを用いたタンパク質力場パラメータの最適化 (2005)
  • Author(s): 榮慶丈, 岡本祐幸
  • Journal Title: 生物物理 45 Pages: 145-148
  • NAID: 110001801950
• [Journal Article] タンパク質のフォールディングシミュレーションから立体構造予測問題に迫る (2005)
  • Author(s): 岡本祐幸, 高田彰二
  • Journal Title: 現代化学 408 Pages: 47-53
• [Journal Article] マルチバーリック・マルチサーマルアンサンブルにおけるレナード・ジョーンズ流体のシミュレーション (2005)
  • Author(s): 奥村久士, 岡本祐幸
  • Journal Title: 物性研究 85 Pages: 341-346
• [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
• [Journal Article] New approach to the first-order phase transition of Lennard-Jones fluids (2004)
  • Author(s): C.Muguruma, Y.Okamoto, M.Mikami
  • Journal Title: J.Chem.Phys. 120 Pages: 7557-7563
  • NAID: 120006545073
• [Journal Article] Prediction of membrane protein structures by replica-exchange Monte Carlo simulations : case of two helices (2004)
  • Author(s): H.Kokubo, Y.Okamoto
  • Journal Title: J.Chem.Phys. 120 Pages: 10837-10847
  • NAID: 120006545074
• [Journal Article] Molecular dynamics simulations in multibaric-multithermal ensemble (2004)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Chem.Phys.Lett. 383 Pages: 403-408
• [Journal Article] Self-assembly of transmembrane helices of bacteriorhodopsin by a replica-exchange simulation (2004)
  • Author(s): H.Kokubo, Y.Okamoto
  • Journal Title: Chem.Phys.Lett. 392 Pages: 168-175
• [Journal Article] Replica-exchange extensions of simulated tempering method (2004)
  • Author(s): A.Mitsutake, Y.Okamoto
  • Journal Title: J.Chem.Phys. 121 Pages: 2491-2504
  • NAID: 120006545075
• [Journal Article] Protein force-field parameters optimized with the Protein Data Bank. I.Force-filed optimizations (2004)
  • Author(s): Y.Sakae, Y.Okamoto
  • Journal Title: J.Theor.Comput.Chem. 3 Pages: 339-358
• [Journal Article] Protein force-field parameters optimized with the Protein Data Bank. II.Comparisons of force fields by folding simulations of short peptides (2004)
  • Author(s): Y.Sakae, Y.Okamoto
  • Journal Title: J.Theor.Comput.Chem. 3 Pages: 359-378
• [Journal Article] Monte Carlo simulations in generalized isobaric-isothermal ensembles (2004)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Phys.Rev.E 70 Pages: 26702-26702
  • NAID: 120006545921
• [Journal Article] Classification and prediction of low-energy membrane protein helix configurations by replica-exchange Monte Carlo method (2004)
  • Author(s): H.Kokubo, Y.Okamoto
  • Journal Title: J.Phys.Soc.Jpn. 73 Pages: 2571-2585
  • NAID: 110001955018
• [Journal Article] Combination of the replica-exchange Monte Carlo method and the reference interaction site model theory for simulating a peptide molecule in aqueous solution (2004)
  • Author(s): A.Mitsutake, M.Kinoshita, Y.Okamoto, F.Hirata
  • Journal Title: J.Phys.Chem.B 108 Pages: 19002-19012
• [Journal Article] Liquid-gas phase transitions studied by multibaric-multithermal Monte Carlo simulations (2004)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: J.Phys.Soc.Jpn. 73 Pages: 3304-3311
  • NAID: 110001979299
• [Journal Article] Multi-overlap molecular dynamics methods for biomolecular systems (2004)
  • Author(s): S.G.Itoh, Y.Okamoto
  • Journal Title: Chem.Phys.Lett. 400 Pages: 308-313
• [Journal Article] Comparisons between a molecular dynamics and hydrodynamics treatment of non-stationary thermal processes in a liquid (2004)
  • Author(s): H.Okumura, D.M.Heyes
  • Journal Title: Phys.Rev.E 70 Pages: 61206-61206
• [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. 307 Pages: 269-283
• [Journal Article] Generalized-ensemble algorithms : enhanced sampling techniques for Monte Carlo and molecular dynamics simulations (2004)
  • Author(s): Y.Okamoto
  • Journal Title: J.Mol.Graphics Modell. 22 Pages: 425-439
• [Journal Article] Monte Carlo simulations in new generalized isobaric-isothermal ensemble (2004)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Trans.MRS-J. 29 Pages: 3783-3786
• [Journal Article] Multibaric-multithermal ensemble simulation for simple liquids (2004)
  • Author(s): H.Okumura, Y.Okamoto
  • Journal Title: Mol.Sim. 30 Pages: 847-852
• [Presentation] Protein folding simulations in generalized ensembles (2007)
  • Author(s): Y. Okamoto(招待講演)
  • Organizer: Mainz Materials Simulation Days 2007 (MMSD 2007)
  • Place of Presentation: Mainz, Germany
• [Book] Lecture Notes in Physics, Springer-Verlag (2008)
  • Author(s): Y. Sugita, A. Mitsutake, & Y. Okamoto (edited by W. Janke)
  • Publisher: Lecture Notes
• [Book] 分子科学者がいどむ12の謎 (2005)
  • Author(s): 岡本祐幸(分担執筆)
  • Total Pages: 235
  • Publisher: 化学同人
• [Book] ベルゲソン 生化学の物理的基礎 (2004)
  • Author(s): 谷村吉隆, 佐藤啓, 依田隆夫, 秋山良, 藤原進, 奥村久士 共訳(P.R.Bergethon著)
  • Total Pages: 603
  • Publisher: シュプリンガー・フェアラーク東京
• [Publications] G.LaPenna, A.Mitsutake, M.Masuya, Y.Okamoto: "Molecular dynamics of C-peptide of ribonuclease A studied by replica-exchange Monte Carlo method and diffusion theory."Chemical Physics Letters. 380. 609-619 (2003)
• [Publications] B.A.Berg, H.Nogichi, Y.Okamoto: "Multi-Overlap Simulations for Transitions between Reference Configurations."Physical Review E. 68. 036126 (2003)
• [Publications] Y.Sakae, Y.Okamoto: "Optimization of protein force-field parameters with the Protein Data Bank"Chemical Physics Letters. 382. 626-636 (2003)
• [Publications] H.Okumura, Y.Okamoto: "Monte Carlo simulations in multibaric-multithermal ensemble."Chemical Physics Letters. 383. 391-396 (2004)
• [Publications] H.Kokubo, Y.Okamoto: "Prediction of transmembrane helix configurations by replica-exchange simulations."Chemical Physics Letters. 383. 397-402 (2004)
• [Publications] K.Murata, Y.Sugita, Y.Okamoto: "Free energy calculations for DNA base stacking by replica-exchange umbrella sampling."Chemical Physics Letters. 385. 1-7 (2004)