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All-Atom Analysis of Dissolution and Aggregation of Proteins in Multi-Component Solutions

Research Project

Project/Area Number 22KF0240
Project/Area Number (Other) 22F21756 (2022)
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeMulti-year Fund (2023)
Single-year Grants (2022)
Section外国
Review Section Basic Section 32010:Fundamental physical chemistry-related
Research InstitutionOsaka University

Principal Investigator

松林 伸幸  大阪大学, 大学院基礎工学研究科, 教授 (20281107)

Co-Investigator(Kenkyū-buntansha) HANSEN STEFAN  大阪大学, 大学院基礎工学研究科, 外国人特別研究員
Project Period (FY) 2023-03-08 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2023: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2022: ¥800,000 (Direct Cost: ¥800,000)
Keywords溶媒和 / 自由エネルギー / 溶液 / 溶解 / 凝集 / MDシミュレーション / 分子間相互作用 / 共溶媒 / 変分定理 / 分布関数理論 / イオン
Outline of Research at the Start

タンパク質の凝集は、アミロイドーシス疾患を引き起こす一因と考えられ、また、抗体医薬などの安定保存の支障ともなっている。本研究では、共溶媒をあらわに取り入れた分子動力学シミュレーションを全原子モデルを用いて実行しエネルギー表示溶液理論との融合手法による自由エネルギー解析を行う。自由エネルギーの成分分割によってタンパク質の溶解性や凝集性を規定する相互作用成分を明らかにし、分子間相互作用のエンジアリングによる凝集制御指針の策定を目指す。

Outline of Annual Research Achievements

共溶媒添加効果の自由エネルギー解析を行なった。アルカンやアルコールの溶媒和自由エネルギーの塩添加による変化を全原子MDシミュレーションとエネルギー表示溶液理論で取り扱った。塩の導入に伴う溶媒和自由エネルギーの変化を溶媒種ごとの寄与に分割することで、塩効果はアニオン種によって規定されることが見出された。さらに、エネルギー表示溶液理論の枠組み内では溶媒和自由エネルギーが系統的に静電成分、van der Waals成分、排除体積成分などの分子間相互作用成分に分割されることに基づいて、共溶媒添加に伴う各相互作用成分の変化と溶媒和自由エネルギーの変化の相関を解析し、共溶媒である塩の種類を変える場合には排除体積成分との相関が最も強いことを見出した。無極性のアルカンおよび極性をもつアルコールに共通し、炭化水素鎖の長さにも依存しない結果であり、長く議論されてきたホフマイスター系列の起源における水密度の役割を示唆する知見となっている。また、共溶媒添加に伴うタンパク質やポリマーの過剰化学ポテンシャルの変化を効率良く計算する手法を開発した。問題とする複数の溶媒条件におけるタンパク質やポリマーの配置の確率密度関数および固定配置における溶媒和自由エネルギーが満たす恒等式を定式化し、タンパク質やポリマーの配置に対する有限サンプリングから来る誤差を最小化することで効率的な過剰化学ポテンシャル変化の計算法を提案した。この手法は全原子モデルに適用可能であり運用の際には溶媒和自由エネルギーの網羅的評価が必要となるが、MDとエネルギー表示溶液理論の融合手法を用いることで溶媒和自由エネルギーの計算を高速化した。生体関連ポリマー系に対して新規手法を適用し、その過剰化学ポテンシャルに対する共溶媒添加効果が現実的な計算負荷で計算できることが明らかになるとともに、塩の特異な配位効果との関連も見出された。

Report

(2 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (29 results)

All 2024 2023 2022 Other

All Int'l Joint Research (3 results) Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 7 results,  Invited: 10 results)

  • [Int'l Joint Research] レーゲンスブルク大学(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] ルント大学(スウェーデン)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] テンプル大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Free-energy decomposition of salt effects on the solubilities of small molecules and the role of excluded-volume effects2024

    • Author(s)
      Hervo-Hansen Stefan、Lin Daoyang、Kasahara Kento、Matubayasi Nobuyuki
    • Journal Title

      Chemical Science

      Volume: 15 Issue: 2 Pages: 477-489

    • DOI

      10.1039/d3sc04617f

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] How ATP suppresses the fibrillation of amyloid peptides: analysis of the free-energy contributions2024

    • Author(s)
      Do Tuan Minh、Horinek Dominik、Matubayasi Nobuyuki
    • Journal Title

      Physical Chemistry Chemical Physics

      Volume: 26 Issue: 15 Pages: 11880-11892

    • DOI

      10.1039/d4cp00179f

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular Dynamics Study of the Antifouling Mechanism of Hydrophilic Polymer Brushes2023

    • Author(s)
      Yagasaki Takuma、Matubayasi Nobuyuki
    • Journal Title

      Langmuir

      Volume: 39 Issue: 37 Pages: 13158-13168

    • DOI

      10.1021/acs.langmuir.3c01552

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arylazopyrazole-Based Photoswitchable Inhibitors Selective for Escherichia coli Dihydrofolate Reductase2023

    • Author(s)
      Himadri S. Sarkar, Takato Mashita, Toshiyuki Kowada, Satoshi Hamaguchi, Toshizo Sato, Kento Kasahara, Nobuyuki Matubayasi, Toshitaka Matsui, and Shin Mizukami*
    • Journal Title

      ACS Chem. Biol.

      Volume: 18 Issue: 2 Pages: 340-346

    • DOI

      10.1021/acschembio.2c00749

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Explaining reaction coordinates of alanine dipeptide isomerization obtained from deep neural networks using Explainable Artificial Intelligence (XAI)2022

    • Author(s)
      Kikutsuji Takuma、Mori Yusuke、Okazaki Kei-ichi、Mori Toshifumi、Kim Kang、Matubayasi Nobuyuki
    • Journal Title

      The Journal of Chemical Physics

      Volume: 156 Issue: 15 Pages: 154108-154108

    • DOI

      10.1063/5.0087310

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] All-atom molecular simulation study of cellulose acetate: amorphous structure and the dissolution of small molecule2022

    • Author(s)
      Matsuba Ryota、Kubota Hiroyuki、Matubayasi Nobuyuki
    • Journal Title

      Cellulose

      Volume: 29 Issue: 10 Pages: 5463-5478

    • DOI

      10.1007/s10570-022-04616-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adsorption Energetics of Amino Acid Analogs on Polymer/Water Interfaces Studied by All-Atom Molecular Dynamics Simulation and a Theory of Solutions2022

    • Author(s)
      Yasoshima Nobuhiro、Ishiyama Tatsuya、Matubayasi Nobuyuki
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 126 Issue: 23 Pages: 4389-4400

    • DOI

      10.1021/acs.jpcb.2c01297

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nonpolarizable Force Fields through the Self-Consistent Modeling Scheme with MD and DFT Methods: From Ionic Liquids to Self-Assembled Ionic Liquid Crystals2022

    • Author(s)
      Ishii Yoshiki、Matubayasi Nobuyuki、Washizu Hitoshi
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 126 Issue: 24 Pages: 4611-4622

    • DOI

      10.1021/acs.jpcb.2c02782

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Surface Area Estimation: Replacing the Brunauer?Emmett?Teller Model with the Statistical Thermodynamic Fluctuation Theory2022

    • Author(s)
      Shimizu Seishi、Matubayasi Nobuyuki
    • Journal Title

      Langmuir

      Volume: 38 Issue: 26 Pages: 7989-8002

    • DOI

      10.1021/acs.langmuir.2c00753

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Crystal Growth of Urea and Its Modulation by Additives as Analyzed by All-Atom MD Simulation and Solution Theory2022

    • Author(s)
      Senri Tanaka, Naoki Yamamoto, Kento Kasahara, Yoshiki Ishii, and Nobuyuki Matubayasi
    • Journal Title

      J. Phys. Chem. B

      Volume: 126 Issue: 28 Pages: 5274-5290

    • DOI

      10.1021/acs.jpcb.2c01764

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constructing a Memory Kernel of the Returning Probability to Efficiently Describe Molecular Binding Processes2022

    • Author(s)
      Kento Kasahara, Ren Masayama, Yuya Matsubara, and Nobuyuki Matubayasi
    • Journal Title

      Chem. Lett.

      Volume: 51 Issue: 8 Pages: 823-827

    • DOI

      10.1246/cl.220236

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular dynamics study of the interactions between a hydrophilic polymer brush on graphene and amino acid side chain analogues in water2022

    • Author(s)
      Yagasaki Takuma、Matubayasi Nobuyuki
    • Journal Title

      Physical Chemistry Chemical Physics

      Volume: 24 Issue: 37 Pages: 22877-22888

    • DOI

      10.1039/d2cp03112d

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperative Sorption on Heterogeneous Surfaces2022

    • Author(s)
      Dalby Olivia P. L.、Abbott Steven、Matubayasi Nobuyuki、Shimizu Seishi
    • Journal Title

      Langmuir

      Volume: 38 Issue: 43 Pages: 13084-13092

    • DOI

      10.1021/acs.langmuir.2c01750

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diffusion theory of molecular liquids in the energy representation and application to solvation dynamics2022

    • Author(s)
      Okita Kazuya、Kasahara Kento、Matubayasi Nobuyuki
    • Journal Title

      The Journal of Chemical Physics

      Volume: 157 Issue: 24 Pages: 244505-244505

    • DOI

      10.1063/5.0125432

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of Water Diffusion in Wide Varieties of Polymers with All-Atom Molecular Dynamics Simulations and Deep Generative Models2022

    • Author(s)
      Kawada Ryo、Endo Katsuhiro、Yasuoka Kenji、Kojima Hidekazu、Matubayasi Nobuyuki
    • Journal Title

      Journal of Chemical Information and Modeling

      Volume: 63 Issue: 1 Pages: 76-86

    • DOI

      10.1021/acs.jcim.2c01316

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyper-mobile Water and Raman 2900 cm<sup>?1</sup> Peak Band of Water Observed around Backbone Phosphates of Double Stranded DNA by High-Resolution Spectroscopies and MD Structural Feature Analysis of Water2022

    • Author(s)
      Suzuki Makoto、Tsuchiko Akira、Tanaka Yoshiyuki、Matubayasi Nobuyuki、Mogami George、Uozumi Nobuyuki、Takahashi Satoshi
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 127 Issue: 1 Pages: 285-299

    • DOI

      10.1021/acs.jpcb.2c06952

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cosolvent effects on peptide aggregation studied with all-atom MD, solvation theory, and variational theorem2024

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      Telluride Science Winter Workshop
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Energetics Analyzed by MD Simulation and Solvation Theory for Partitioning Functions of Molecular Aggregates with Nanoscale Inhomogeneity2023

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      26th IUPAC International Conference on Chemical Thermodynamics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Free Energetics of Solvation Analyzed through All-Atom MD Simulation and a Density-Functional Method2023

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      The 6th International Conference on Molecular Simulation
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] All-Atom Analysis of Intermolecular Interactions in Polymeric Materials: Water Absorption and Mutual Miscibility2023

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      International Conference on Chemistry and Material Science
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 溶液系における密度汎関数理論とエネルギー表示2023

    • Author(s)
      松林伸幸
    • Organizer
      電気化学界面シミュレーションコンソーシアム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Exploring diverse classes of solvation through endpoint density-functional for free energy2023

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      ACS SPRING 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 溶媒和論の普遍化に基づくソフト分子集合系における物質分配機能の全原子解析2022

    • Author(s)
      松林 伸幸
    • Organizer
      JST-CRDS俯瞰ワークショップ
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 分子シミュレーションによる結晶成長および結晶形状制御の全原子解析2022

    • Author(s)
      松林 伸幸
    • Organizer
      日本水・蒸気性質協会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Solvation energetics of biomolecules analyzed by all-atom molecular dynamics simulation and a solution theory2022

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      International Conference on Physical Chemistry, The Annual Meeting of Physical Chemistry Division of Indonesian Chemical Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] MD-DFT Approach to the Electrical Conductivity of Ionic Liquid2022

    • Author(s)
      Nobuyuki Matubayasi
    • Organizer
      The International Association for the Properties of Water and Steam 2022 Annual Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2022-04-28   Modified: 2024-12-25  

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