A theoretical verification of the ligand-binding-pathway hypothesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07021
• 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: Terada Tohru 東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (40359641)
• Research Collaborator: NEGAMI Tatsuki 東京大学, 大学院農学生命科学研究科, 特任研究員
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 分子動力学シミュレーション / タンパク質 / リガンド / パスウェイ / 粗視化モデル / 自由エネルギープロファイル / マルコフ状態モデル / transition path theory

Outline of Final Research Achievements

I performed many runs of a coarse-grained molecular dynamics simulation for a protein-ligand system, where the ligand molecules were randomly placed around the protein. I constructed a Markov state model from the trajectories. Furthermore, I analyzed the model based on the transition path theory to find the transition state and ligand-binding pathways. As a result, it was shown that the transition state is located around the rim of the substrate-binding pocket and the ligand-binding pathways that have large contributions to the ligand binding tend to go along the grooves on the protein surface. This result supports the ligand-binding-pathway hypothesis we have proposed.

Free Research Field

計算生物物理学