2021 Fiscal Year Final Research Report
Exploring a Guideline for Inhibiting the Peptide Aggregation through All-Atom Analysis of Cosolvent Effect
| Project/Area Number |
19H04206
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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 62010:Life, health and medical informatics-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 凝集 / 溶媒和自由エネルギー / 共溶媒 / エネルギー表示溶液理論 / MDシミュレーション / 多変量解析 / リガンド結合 / 分子間相互作用 |
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| Outline of Final Research Achievements |
The cosolvent effects on the equilibria of peptide aggregation and ligand binding were studied on the basis of a statistical-mechanical theorem that the derivative of the excess chemical potential with respect to the cosolvent concentration is determined by the corresponding derivative of the solvation free energy averaged over the solute configurations. The solvation free energies in the pure-water solvent and the mixed solvent with a cosolvent were computed with all-atom MD simulation and the energy-representation theory of solvation, and it was observed for a peptide and its aggregates that the solvation becomes more favorable with addition of the urea or DMSO cosolvent. The extent of stabilization was smaller for larger aggregates, which implies that these cosolvents inhibit the formation of an aggregate. The roles of such interaction components as the electrostatic, van der Waals, and excluded-volume were discussed with correlation analyses.
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| Free Research Field |
理論計算化学
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| Academic Significance and Societal Importance of the Research Achievements |
凝集体形成やリガンド結合の平衡定数に対する共溶媒効果は溶媒和自由エネルギーの変化のみで記述できるという定理に基づき、溶媒和自由エネルギーの網羅的解析によって凝集体形成能の共溶媒添加に伴う変化の系統的な解析を可能としたことに学術的な意義がある。アミロイドーシス疾患に関わるペプチド系を検討対象として現実的な設定における共溶媒添加効果を定量化し、共溶媒効果を規定する分子間相互作用成分を同定したことに社会的な意義がある。
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