Signal Transduction Process of G-Protein Coupled Receptor (GPCR) Studied by Molecular Dynamics Simulation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06164
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biophysics
• Research Institution: University of Tsukuba
• Principal Investigator: HARADA Ryuhei 筑波大学, 計算科学研究センター, 准教授 (60612174)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Gタンパク質共役受容体 / 分子動力学シミュレーション

Outline of Final Research Achievements

G Protein Couple Receptor (GPCR) is an important membrane protein that transfers several signals from the outer to inner membrane upon the ligand binding. However, its mechanism of signal transduction process has not revealed yet. In the present study, We have developed a set of computational methods (path sampling methods) to address the signal transduction process of GPCR. In more detail, a set of two enhanced sampling methods called "Parallel Cascade Selection Molecular Dynamics (PaCS-MD)" and "Outlier Flooding Method (OFLOOD)" has been combined as a hybrid path search method and it was applied to the GPCR system. In the current status, we are now analyzing trajectories (transition path trajectories related to the signal transduction of GPCR) generated by the hybrid conformational sampling method.

Free Research Field

計算生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究において, GPCRなどの巨大システムの反応経路探索に適用可能な計算手法を開発したことで, GPCR以外の重要な生体分子にも適用可能な堅牢な方法論を提供することができた. 開発手法は, 様々な研究者に利用可能な様に一般公開を進めており, 今後社会還元していく予定である. また, GPCRは創薬設計においてレセプターとしても注目されている重要なタンパク質であり, 細胞内外におけるシグナル伝達経路のメカニズムの解明が進むことは, 合理的な新薬設計に与える影響も大きいと考えられ, 更なる社会還元が期待される.