Engineering antibody stability using molecular simulations and machine learning
| Project/Area Number |
17K18113
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biophysics
Life / Health / Medical informatics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kuroda Daisuke 東京大学, 大学院工学系研究科(工学部), 講師 (60756732)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Discontinued (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 抗体設計 / タンパク質工学 / 分子シミュレーション / 機械学習 / データベース / 熱安定性 / 凝集性 / 物理化学測定 |
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| Outline of Final Research Achievements |
The purpose of this study was to develop a method to control the physical stability of antibodies using computational technology.
(1) We have created virtual libraries containing more than 6000 mutants by mutagenesis experiments in a computer. we have experimentally confirmed by using a differential scanning calorimeter and ELISA that there are mutants with improved thermal stability while maintaining affinity.
(2) We have compared amino acid sequences of a stable antibody and an unstable antibody, and mutations for stability improvement were identified. We were able to clarified stabilizing factors by using the molecular simulation. Based on the mutant information thus obtained, a prediction model for evaluating antibody stability by machine learning was constructed.
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| Academic Significance and Societal Importance of the Research Achievements |
物質を分子レベルで自在に設計・制御する技術は、多くの研究者にとって「夢の技術」である。蛋白質の物性を自在に制御できるようになれば、基礎研究のみならず、蛋白質医薬品や新規素材開発への応用など、その社会へのインパクトも大きい。代表者が本助成により開発してきた計算・情報科学技術と、蛋白質工学や物理化学測定の実験手法を融合させることで、新たな分子操作技術の開発へ向けた次世代蛋白質工学への展開が期待できる。本研究で開発に取り組んだ、生体分子の物性を自在に制御するコンピュータシステムにより、将来的には抗体の完全人工設計や人工蛋白質の創製など、「夢の技術」の実現につながると考えている。
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Report
(2 results)
Research Products
(15 results)
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[Journal Article] Assessing the Heterogeneity of the Fc-Glycan of a Therapeutic Antibody Using an engineered FcγReceptor IIIa-Immobilized Column2018
Author(s)
Kiyoshi M, Caaveiro JMM, Tada M, Tamura H, Tanaka T, Terao Y, Morante K, Harazono A, Hashii N, Shibata H, Kuroda D, Nagatoishi S, Oe S, Ide T, Tsumoto K, Ishii-Watabe A
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Journal Title
Scientific Reports
Volume: 8:3955
Issue: 1
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Structures of the prefusion form of measles virus fusion protein in complex with inhibitors2018
Author(s)
Hashiguchi T, Fukuda Y, Matsuoka R, Kuroda D, Kubota M, Shirogane Y, Watanabe S, Tsumoto K, Kohda D, Plemper RK, Yanagi Y
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Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: 115(10)
Issue: 10
Pages: 2496-2501
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Structural, physicochemical and computational analysis to reveal the mechanism of recognition of phosphorylated antigen by an antibody2018
Author(s)
KAWADE, Raiji; AKIBA, Hiroki; NAKAKIDO, Makoto; KURODA, Daisuke; MARUYAMA, Toshiaki; OKUMURA, Shigeru; ENTZMINGER, Kevin; CAAVEIRO, Jose; TSUMOTO, Kouhei
Organizer
日本化学会第98春季年会
Related Report
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