Developing a method for analyzing biomolecular interactions via multivalent ligand binding

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12112
• 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: Kitasato University
• Principal Investigator: Noto Kaori 北里大学, 一般教育部, 准教授 (20361818)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖鎖 / 分子認識機構 / 多価結合 / 分子動力学 / 量子化学計算 / 付着因子 / 毒素

Outline of Final Research Achievements

Protein－glycan interactions are widespread in biology and play a central role in many important biological events, such as bacterial infection. However, the interactions between proteins and glycans are intrinsically weak. To compensate for this limitation, multimeric protein-glycan interactions have been reported in several systems, such as adhesion factors of pathogenic bacteria and early stages of infection by verotoxins to target cells.
To elucidate the multivalent interaction between glycans and proteins in the adhesin FimH, and the mechanism of multivalent glycan recognition by verotoxin, detailed analyses of the interaction between glycans and the proteins using MD simulation as well as quantum chemical calculations were conducted. Through this study, a new simulation method was developed to evaluate the recognition specificity of multivalent binding of ligands in vivo.

Free Research Field

計算化学

Academic Significance and Societal Importance of the Research Achievements

生体内で細胞や特定の器官が高度に識別される際，細胞膜の構成成分として広く分布する様々な糖鎖の認識特異性が使われているが，糖鎖とタンパク質間の親和性自体は強くないため，糖鎖が多価で結合することで親和性を高めていることが示唆されている．このような生体内での多価結合の詳細に関する理論は未だ確立されていない．生体内の糖鎖構造決定は難しく，実験的な解明は限られているため，生体内多価相互作用を扱えるシミュレーション手法は社会的にニーズがある．このシミュレーションによって明らかになる基礎情報は学術的に意義があると共に，新規薬物，薬物輸送糖鎖修飾分子の設計指針となる．