Studies on the transition state of protein folding by means of correlation analysis between the folding rate and the native structure

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biophysics
• Research Institution: The University of Tokyo
• Principal Investigator: Kuwajima Kunihiro 東京大学, 大学院理学系研究科(理学部), 名誉教授 (70091444)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: フォールディング / 速度論 / 遷移状態

Outline of Final Research Achievements

In this study, (1) a standardized protein folding database, in which the folding rate constant of all listed proteins are calculated at the standard temperature (25°C), has been constructed and opened on the internet homepage. (2) The correlations between the Φ values, which represent the degree of structural formation in the transition state of folding, and different structure-based properties of proteins were analyzed, and the relationships between the structure-based properties and the critical structure in the transition state were discussed. (3) Academic literatures concerning the relationships between the folding rate constant and various structure-based properties were investigated, and it has been found that the two-state and the non-two-state folding reactions of proteins apparently seem very different, but are based on essentially the same physical principles.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

蛋白質フォールディング機構の研究は，蛋白質の間違ったフォールディングによって引き起こされる，ヒトの様々なフォールディング病（アルツハイマー病，白内障，クロイツフェルト・ヤコブ病，パーキンソン病，II型糖尿病など多数）などの原因解明や治療法の構築の応用研究に役立つと期待される，基盤的な研究である。本研究で構築されたデータベースは，蛋白質フォールディングの計算機シミュレーションや理論研究の研究者によって，広く活用されることが期待される。本研究で実施された，Φ値やフォールディング速度と構造特性との間の相関解析は，本データベースを活用するための事例研究として用いることも出来る。