Design principles of protein structures underlying allosteric regulation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K05518
• 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: Hiroshima University
• Principal Investigator: Togashi Yuichi 広島大学, 統合生命科学研究科(理), 准教授 (50456919)
• Co-Investigator(Kenkyū-buntansha): FLECHSIG HOLGER 金沢大学, ナノ生命科学研究所, 特任助教 (00758964)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: アロステリック制御 / 分子内情報伝達 / 構造機能相関 / 生体高分子 / タンパク質 / 粗視化分子動力学 / 進化的最適化 / 計算生物物理学

Outline of Final Research Achievements

We aimed to better understand the design principles and function of allosteric communication. We followed hybrid approaches: 1. designing artificial model structures through evolutionary optimization, and comparing their dynamical properties with those obtained for several allosteric proteins; 2. exhaustively constructing models for a number of known protein structures and analyzing mechano-transmission properties and relevant structural features. We found that already simple mechanical networks reproduce the pattern of communication characteristic for real allosteric proteins. Hence, a new class of structurally resolved model systems of protein allostery was established. Using the developed models, we are currently investigating topical aspects of protein allostery, applying concepts of information theory and stochastic thermodynamics. Moreover, we extended the modeling and analysis to multi-domain structures, and also investigated the validity and robustness of the modeling scheme.

Free Research Field

計算生物物理学

Academic Significance and Societal Importance of the Research Achievements

タンパク質の中には、分子内のある部分での変化（例えば別の分子の結合）が、そこから離れた部分への影響（例えば酵素活性の変化）を引き起こすものがあります。これを実現するためには、２つの離れた部分の間で、何らかの分子構造の変化を介して「情報」を伝える必要があります。本研究では、現実のタンパク分子構造と、情報を伝えるように「進化」させた人工的構造とを用いて、シミュレーションにより、構造変化の伝わり方と分子構造との関係を解析しました。