2022 Fiscal Year Final Research Report
Complex structure and affinity prediction among cancer vaccine peptides and immune related proteins
| Project/Area Number |
20H03229
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | University of Hyogo |
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Principal Investigator |
Kamiya Narutoshi 兵庫県立大学, 情報科学研究科, 特任教授 (80420462)
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| Co-Investigator(Kenkyū-buntansha) |
織田 昌幸 京都府立大学, 生命環境科学研究科, 教授 (20318231)
伊藤 暢聡 東京医科歯科大学, 難治疾患研究所, 教授 (40361703)
Bekker Gerardu 大阪大学, 蛋白質研究所, 特任助教(常勤) (80813758)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 分子動力学シミュレーション / 構造予測 / 親和性予測 |
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| Outline of Final Research Achievements |
Predictions of the tertiary structure, thermal stability and affinity of immune-related proteins and cancer antigen peptides, either the binary-complex type (consisting of HLA and peptide) or the ternary-complex type (consisting of HLA, peptide, and T cell receptor), were carried out using molecular dynamics (MD) simulations. The most stable structure in terms of its free-energy and a binding pathway between HLA and the antigen peptide were obtained using multicanonical MD calculations. Next, the affinity was predicted using MD simulations along the pathway. In addition, we executed affinity measurement and crystallographic experiments, validating our simulation results. Subsequently, the ternary-complex was predicted by MD calculations. Finally, the stability estimation revealed that our predicted complexes were included stable structures. Taken together, our methods are useful to analyze the interaction of immune-related proteins in detail.
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| Free Research Field |
生物物理学
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| Academic Significance and Societal Importance of the Research Achievements |
安定性を評価するのに最適な物理量である自由エネルギーを用いた複合体構造の予測法を開発し、タンパク質-ペプチドやタンパク質-タンパク質複合体構造の予測に成功した点で、物理化学的に大きな意義がある。研究対象の癌抗原ペプチドはT細胞を活性化し、腫瘍細胞への攻撃性が獲得できるが、患者毎にペプチドの特異性や親和性、即ち、ペプチドの有効性が異なることが問題である。本研究手法を用いることにより、この問題を克服し、個々に有効なペプチドを提案できれば、個別で高精度な医療が実現することになり、社会的な意義は大きい。
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