3D Structure prediction of glycan clusters and its application for vaccine design

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12229
• 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: National Institutes of Biomedical Innovation, Health and Nutrition (2020-2021); Institute of Physical and Chemical Research (2019)
• Principal Investigator: Re Suyong 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 AI健康・医薬研究センター, 主任研究員 (50390670)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 糖鎖クラスタ / 立体構造予測 / 分子動力学計算 / エピトープ / ラッサ熱

Outline of Final Research Achievements

The protein glycosylation affects a protein-antibody interaction, but a little is known about the effect because of the diverse structures and interactions of glycans. Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus. Using molecular dynamics simulations, we show that the glycans form distinct clusters to non-uniformly shield the protein surface. We integrated the simulation results with existing sequence- and structure-based epitope prediction methods and successfully recovered known protein epitopes and even predicted new ones. This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.

Free Research Field

計算化学

Academic Significance and Societal Importance of the Research Achievements

細胞表面を覆う糖鎖はがんや感染症など多くの病気と関係する。しかし、複雑で柔らかい糖鎖構造を実験で見るのは未だ難しい。特に複数の糖鎖が集まった時にどの様な構造をとるかはほとんど知られていなかった。本研究成果は糖鎖集合のクラスタ形成を原子解像度で示すもので、従来仕組みのわからなかった高度な糖鎖機能を説明する新たな視点を与える。さらに、糖鎖を標的とするワクチン開発にも役立つと期待され、学術的にも社会的にも意義は大きい。