2024 Fiscal Year Final Research Report

Building a Predictive Mathematical Platform for RNA Modification Structure and Function

Research Project

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Project/Area Number	23K24941
Project/Area Number (Other)	22H03686 (2022-2023)
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Multi-year Fund (2024) Single-year Grants (2022-2023)
Section	一般
Review Section	Basic Section 62010:Life, health and medical informatics-related
Research Institution	National Institute of Advanced Industrial Science and Technology (2024) Nagoya University (2022-2023)
Principal Investigator	Koseki Jun 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (20616669)
Co-Investigator(Kenkyū-buntansha)	今野雅允国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (80618207)
Project Period (FY)	2024-04-01 – 2025-03-31
Keywords	RNA修飾 / 構造変化 / 機能変化 / 理論科学 / 位相幾何学
Outline of Final Research Achievements	Because of the strong correlation between structure and function in biomolecules, it has been reported that chemical modifications can induce structural changes and alter molecular interactions, thereby affecting biological function. We developed a predictive platform based on persistent homology, a method from topological data analysis, to extract how subtle structural changes - such as the presence or absence of chemical modifications - can lead to significant changes in molecular interactions and overall molecular structure. This platform can also detect changes in hydrogen bonding and CH-π interactions that mediate the propagation of structural changes throughout the molecule. As a result, our approach enables the quantitative interpretation and prediction of the relationship between structure and function in modified biomolecules.
Free Research Field	理論構造化学
Academic Significance and Societal Importance of the Research Achievements	生体内分子の『構造と機能』の関係性を抽出するための手法として、Dynamical Analysis of Interaction and Structural changes (DAIS)法を確立した。本手法はウイルスの感染力に及ぼす影響や、アミノ酸変異がもたらす機能変化、薬剤耐性等に応用可能である。実際にRNA修飾の機能変化のみにかかわらず、SARS-CoV-2増殖を抑制するレムデシビルの薬剤耐性要因の可能性を示すことにも成功しており、近年問題視されているウイルス感染症に対するアミノ酸変異の影響を考慮した臨床研究分野にも寄与できる手法として確立できたため、その社会的意義は大きいと考えられる。