A stochastic description of protein conformational transition by global landscape calculation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Nagoya University
• Principal Investigator: Terada Tomoki 名古屋大学, 工学研究科, 准教授 (20420367)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: タンパク質の構造転移 / アロステリック転移 / 粗視化モデル / 分子動力学計算

Outline of Final Research Achievements

Recent developments in experimental techniques have revealed that proteins not only have a unique native structure but also serve their functions through conformational transitions between multiple structures. In this study, we constructed the chameleon model as a coarse-grained model to describe protein conformational transitions and to clarify the design principles of molecular-level interactions that enable conformational transitions, and applied it to multiple proteins that undergo conformational transitions in various ways. In particular, for adenylate kinase, the temperature dependence of the conformational transition rate obtained from free energy landscape calculations well explains the temperature dependence of the enzymatic reaction rate, confirming that we have successfully constructed a valid model.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

タンパク質は天然条件下では決まった構造をとるが、機能を果たすさいには複数の構造のあいだで構造転移を起こす。例えばタンパク質を人工的に改変して、酵素反応の速度を上げようとするさいには、この反応の途中で起こる構造転移の速度を制御する必要がある場合がある。このような場合に、タンパク質のどの部分をどのように改変すべきかを知るためには、構造転移の経路を計算機上で多数生成して、それらを確率的に扱う必要がある。本研究ではそのような用途で用いられるカメレオンモデルを構築し、実験事実との比較からモデルの妥当性を示した。