Funnel-gas model for studying protein complex formations under crowded environment

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K05246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological physics/Chemical physics/Soft matter physics
• Research Institution: Osaka University
• Principal Investigator: Kikuchi Macoto 大阪大学, サイバーメディアセンター, 教授 (50195210)
• Research Collaborator: Shirai Nobu C. ; Tada Yoshikatsu
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: タンパク質折れたたみ / 天然変性タンパク質 / ファネル描像 / αシヌクレイン / 分子混雑 / 繊維形成

Outline of Final Research Achievements

As a new coarse-grained protein model for investigating the folding and complex formations under the crowded environment, we proposed "funnel-gas model", in which proteins are treated as particles having funnel-like energy structures.
Firstly, we found theoretically that the excluded-volume effect of the crowded molecules can be taken into account rigorously in the effective free energy of proteins. Applying this theory to two model proteins, we showed that the crowded molecules suppress the extended conformations among the denatured states and as a result the native conformations are stabilized. Secondly, using the model, we showed that the fibril formation of alpha-synuclein is enhanced by the molecular crowding effect. Finally, we proposed a random structural network model for describing the protein folding, and showed that the native states which have mutationally robust funnel-like energy structures are very rare.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

タンパク質は複雑な分子であるため、熱平衡状態の計算は現在の計算機をもってしても難しい。特に繊維形成などタンパク質が複合体を形成する機構を調べるためには、計算量が少ない粗視化モデルが必要である。本課題ではタンパク質をひとつの粒子として扱いつつ、その特徴である「ファネル的エネルギー構造」を取り入れたモデルを提案した。このモデルでは現実の細胞環境で重要となる分子混雑の効果がタンパク質の有効自由エネルギーに繰り込まれるため、少ない計算量で複合体形成をシミュレーションでき、様々な応用が期待できる。その一例として、天然変性タンパク質の繊維形成機構を調べ、実験結果の解釈への示唆を行ったのは重要な結果である