A computational structural study on recognition of the influenza virus hemagglutinin by hterosubtypic monoclonal antibody
| Project/Area Number |
17K08069
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Veterinary medical science
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| Research Institution | Hokkaido University |
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Principal Investigator |
Igarashi Manabu 北海道大学, 人獣共通感染症国際共同研究所, 准教授 (10374240)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | インフルエンザウイルス / 抗体 / 分子動力学 / 分子モデリング / 分子間相互作用 / 結合自由エネルギー / 親和性 / インフルエンザ / ウイルス / 分子動力学計算 / 分子設計 / 計算科学 |
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| Outline of Final Research Achievements |
We are aiming to design a neutralizing antibody against escape mutant strains and/or multiple HA subtypes of influenza A viruses. In this study, we tried to modify the binding ability of S139/1, a cross-reactive neutralizing monoclonal antibody against HAs, using the binding free energy obtained from molecular dynamics simulations as an indicator. For the HA from A/Victoria/3/75 (H3N2) used in this study, only amino acid substitutions on S139/1 was unable to restore the recogniton ability of S139/1 against escape mutants, suggesting that the replacement of an entire CDR loop are required.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の最終目的は、抗体の親和性・特異性を制御するための論理的分子設計手法の確立である。このような立体構造を基盤に既存抗体の親和性・特異性を改変する技術は、様々な人獣共通感染症の診断・治療研究へ幅広く応用されることが想定される。本課題の成果はその設計手法の一助となると考えられる。
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Report
(7 results)
Research Products
(10 results)
