Development and application of a conformational search model to predict three-dimensional structural ensembles of glycans

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00415
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Re Suyong 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (50390670)
• Research Collaborator: SUGITA Yuji ; YAMAGUCHI Yoshiki ; GALVELIS Raimondas
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 糖鎖 / 立体構造アンサンブル / 分子動力学シミュレーション / レプリカ交換法 / 拡張アンサンブル法

Outline of Final Research Achievements

Glycan is a biomolecule in which monosaccharides are linked through glycosidic linkages. Glycans bind to proteins as well as lipids and are involved in a various biological process, and also relate to diseases such as viral infections. Three-dimensional structural information of glycans is essential for understanding and controlling glycans' functions. However, 3D-structures of glycans are difficult to obtained by experiment due to the complexity and flexibility of their structures.
In this work, we present a powerful means to computationally predict 3D-structural ensembles (a structural model consisting of multiple three-dimensional structures that represent flexible biomolecular structures) of glycans. We show that, using a combined method of replica exchange molecular dynamics with metadynamics, it is possible to enhance the conformational sampling of glycans and to predict 3D-structural ensembles of N-glycans in high precision.

Free Research Field

計算化学、生物物理、バイオインフォマティクス、情報学

Academic Significance and Societal Importance of the Research Achievements

DNAやRNA、タンパク質については、構造生物学的な研究により機能と構造との関係が次々と明らかになり、それらの理解・情報を用いて薬剤分子も設計されている。一方で、糖鎖の構造は柔らかく複雑であるため、機能に関係する構造情報を得るのが極めて難しい。本研究成果は、計算化学の手法を用いた糖鎖立体構造予測の強力な手段を提供するもので、糖鎖の構造―機能相関を解明する推進力となるとともに、新たな創薬ターゲットの創出にも繋がると期待する。