Prediction of protein deterioration and optimal bio-protectants by measuring and computing water molecular dynamics

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K18684
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 19:Fluid engineering, thermal engineering, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Shirakashi Ryo 東京大学, 生産技術研究所, 教授 (80292754)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 生体系の水 / 分子回転緩和時間 / 分子動力学 / 誘電分光 / 生体保護物質 / 水和殻 / 保護物質水溶液

Outline of Final Research Achievements

Water as general solvent of protein and bio-protectants solutions dominates the stability of protein. Especially molecular rotational relaxation time of water directly corresponds to the relaxation time of protein deterioration. In this study, to control the water relaxation time by solutes, saccharides or proteins, the mechanism that defines the water relaxation time in such solutions was studied. The water relaxation time in lysozyme or saccharides solutions calculated by molecular dynamics simulation (MD), which is in good agreement with the relaxation time measured by dielectric spectroscopy, revealed that the water relaxation time is ruled by; 1)the rotational relaxation time of electric field in solute hydration layer, 2) residence time of water in hydration layer, and 3)the volume ratio of solute hydration layer, and that these phenomena could be controlled by solute properties and its concentration.

Free Research Field

熱工学

Academic Significance and Societal Importance of the Research Achievements

バイオ薬剤の多くは，薬効分子が水溶液中に存在している．液体中の薬剤は，劣化が進みやすいため，経験的に選択した保護物質を添加して有効期間を延ばしている．本研究の成果は，薬剤劣化の鍵となる溶媒である水分子の分子運動（回転緩和時間）を制御する指針を見出した点で保護物質の選択・設計に資する．また，含水材料のマクロ特性を左右する水分子の回転緩和時間に焦点を当て，分子計算と測定が一致することを示し，分子スケールの現象との関係を明らかにした．その成果は，保護物質分子に限らず，水の介在で特性が変化する材料の選択や評価を高い信頼性で可能にする点で学術的にも意義がある．