Mechanism of Molecular Levarage

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H03661
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokai University
• Principal Investigator: Goto Shinya 東海大学, 医学部, 教授 (50225653)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 血小板 / 膜糖蛋白 / コンピューター / 分子動力学

Outline of Final Research Achievements

The integrated model of Integrin αIIbβ3 (platelet GPIIb/IIIa) was developed by combining the extracellular domain adopted from crystal structure and the transmembrane and intracellular domain obtained by NMR. The trans-membrane domain was settled into the phosphatidylcholine (POPC) lipid bilayer model. The position coordinates and velocity vectors of all atoms and water molecules around them were calculated by molecular dynamic simulation with the use of CHARMM (Chemistry at HARvard Macromolecular Mechanics) force field in every 2 x 10－15 sec. By using this newly developed model. the relationship between dynamic structural changes in extra-cellular domain of integrin αIIbβ3 could be understood from the dynamic structural fluctuation in intra-cellular domain of integrin αIIbβ3.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

細胞は外部環境に適応して生理機能を変化させる。細胞機能の変化は各種膜蛋白の細胞ガイドメインの構造に依存している。外部環境の変化による細胞内環境の微小変化が細胞外ドメインの構造と機能を大きく変化させるメカニズムを分子動力学計算にて物理卓的に解明するための方法の基盤を作成した。医学・生物学に広く応用可能な技術となる。