Computational design and experimental validation of a novel heme-binding protein with desired structure and function

• Project/Area Number: 18K14660
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Moriwaki Yoshitaka 東京大学, 大学院農学生命科学研究科(農学部), 助教 (70751303)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 蛋白質科学 / 計算科学 / 人工タンパク質 / タンパク質デザイン / ヘムタンパク質 / タンパク質科学 / 機械学習

Outline of Final Research Achievements

This research aims to explore and demonstrate design theories for creating protein structures and functions using computational science. We also aimed to achieve the design of a de novo protein with a heme-transfer functionality. After obtaining protein 3D structural information around the heme-binding site necessary for heme-binding by statistical analysis and identifying them as structural parts, we used a protein structure-building software called "Topobuilder" to create new protein structural backbones with the functional motifs.

Academic Significance and Societal Importance of the Research Achievements

ほとんどすべての生物は蛋白質を利用し自身の生命活動を維持している。その蛋白質の機能はそれぞれ固有の立体構造に起因している事が多いため、人工的に指定した蛋白質の構造をとるようなアミノ酸配列を合理的に設定できるようになることは、創薬を含むあらゆる生命活動を人工的に制御できるようになることが予想される。