Molecular Recognition Mechanism of RNA aptamer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Nihon University
• Principal Investigator: YAMAGISHI Kenji 日本大学, 工学部, 准教授 (90460021)
• Co-Investigator(Kenkyū-buntansha): 坂本 泰一 千葉工業大学, 先進工学部, 教授 (40383369) ; 石川 岳志 鹿児島大学, 理工学域工学系, 教授 (80505909)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RNAアプタマー / 計算化学 / 分子シミュレーション / 分子動力学計算 / フラグメント分子軌道計算 / 核酸

Outline of Final Research Achievements

We performed ab initio FMO calculation for the RNA aptamer-hFc1 complex to understand the high affinity and specificity of the RNA aptamer. We analyzed the intermolecular interactions between each nucleotide of the aptamer and each amino acid of hFc1 using FMO-IFIE analysis. The G7 nucleotide shows the strongest interaction energy with hFc1 among all groups. In particular, ionic interaction of the phosphate group of the G7 nucleotide with Lys340 results in a robust electrostatic interaction between the RNA aptamer and hFc1. We furthermore performed molecular dynamics simulation for the RNA aptamer-hFc1 complex with and without Ca2+ ions in a solvent. Only in the absence of Ca2+ ions, the RMSD increased and the structure of the aptamer changed from the initial structure. This result indicates that Ca2+ ions play a role in maintaining the conformation of the RNA aptamer to the binding form.
This study provides physicochemical insights into the binding of the RNA aptamer to hFc1.

Free Research Field

計算化学

Academic Significance and Societal Importance of the Research Achievements

本研究により、論理的根拠に基づいたRNAアプタマーの設計が可能になり、アプタマー開発の大きな部分を占めていた配列の最適化や修飾基の導入工程を飛躍的に効率化させることができる。今までの方法では予測できなかった修飾を加えることで、活性を向上・変化させることも可能となり、画期的なRNAアプタマーの開発につながる。これにより、これまで有効な治療法のなかった疾患に対する治療薬の開発も期待でき、社会的にも大きな意義を持つ。