2022 Fiscal Year Final Research Report
Elucidation of dependence of secondary structure on the formation of protein structure and development of new forcefield incorporating effects of secondary structure
| Project/Area Number |
19K06589
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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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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Hiroshima City University |
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Principal Investigator |
Takano Yu 広島市立大学, 情報科学研究科, 教授 (30403017)
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| Co-Investigator(Kenkyū-buntansha) |
近藤 寛子 北見工業大学, 工学部, 助教 (60700028)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 水素結合 / 二次構造 / 分子力場 / 蛋白質 / 分子動力学シミュレーション / 密度汎関数法 |
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| Outline of Final Research Achievements |
To develop a new force field function and its parameters that depend on the protein structure, in particular secondary structure, hydrogen bond (H-bond) energies were calculated for representative secondary structures using a combination of quantum chemical calculations and the Negative Fragmentation Approach (NFA) and compared with the classical force field. Our computational results suggest that the destabilization of the H-bond is attributed to the depolarization caused by the adjacent residue of the helical backbone connecting the H-bond donor and acceptor. Based on the findings from our computational results, a model was constructed in which the atomic partial charges of the N-H and C=O groups of the backbone peptide groups forming H-bonds are changed by the neighboring peptide groups, respectively, reproducing the H-bond energies of alpha-helices and 3_10-helices given by the NFA computation. We expect that this modification could lead to more reliable MD simulations.
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| Free Research Field |
計算化学
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| Academic Significance and Societal Importance of the Research Achievements |
タンパク質の機能発現の理解に長時間の分子動力学シミュレーションが必須なツールである。しかし、そこで使われる分子力場の精度に問題がある。本申請では、「アミノ酸主鎖の水素結合エネルギーには高次構造依存性がある」といった現象にもとづき、量子化学計算を用いてタンパク質構造形成に重要である水素結合の高次構造依存性の起源を明らかにし、高次構造に依存する新規な力場関数とパラメータの開発を目的に研究を進めた。その結果、代表的な二次構造であるヘリックスに関して、隣接するカルボニル基およびアミノ基の影響よりペプチド結合が脱分極し、水素結合が不安定化されることを明らかにし、分子力場の精度の改良に重要な知見を得た。
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